Frontiers in Pharmacology最新文献

{"title":"A systematic review and meta-analysis on the efficacy and safety of finerenone in the progression of heart failure.","authors":"Shengtian Peng, Peipei Li, Zhixi Yu, Beibei Du, Ping Yang","doi":"10.3389/fphar.2025.1575307","DOIUrl":"10.3389/fphar.2025.1575307","url":null,"abstract":"<p><strong>Aims: </strong>Finerenone, a kind of mineralocorticoid receptor antagonist (MRA), may benefit heart failure (HF) patients as MRAs are established effective therapies for HF. Many studies have confirmed the drug's effectiveness in treating kidney disease. However, the efficacy and safety of finerenone on HF remain unclear. Therefore, this systematic review and meta-analysis was conducted to assess the preliminary efficacy and safety of finerenone in HF treatment.</p><p><strong>Methods: </strong>This systematic review and meta-analysis included randomized controlled trials (RCTs) involving adults with heart failure, diabetes, or chronic kidney disease (CKD) treated with finerenone. The major outcomes were the risk of HF occurrence or worsening and hospitalization due to HF, whereas the secondary outcomes included cardiovascular death and all-cause mortality. Data were extracted and analyzed following PRISMA guidelines, and risk of bias was evaluated using the Cochrane Handbook. This review was registered with the International Prospective Register of Systematic Reviews (PROSPERO; CRD42024612580).</p><p><strong>Results: </strong>Six RCTs (n = 21, 295) were included. Finerenone was associated with a lower risk of HF occurrence or worsening and hospitalization due to HF than placebo [risk rate (RR): 0.81; 95% confidence interval (CI): 0.76-0.87; P < 0.00001]. However, no prominent differences were found in cardiovascular death (RR: 0.93; 95% CI: 0.83-1.03; P = 0.18) or all-cause mortality (RR: 0.94; 95% CI: 0.87-1.02; P = 0.11). Safety analysis indicated a reduced risk of serious adverse reactions (RR: 0.93; 95% CI: 0.90-0.98; P = 0.005) and discontinuation of the study medication due to adverse events (RR: 1.14; 95% CI: 1.01-1.30; P = 0.04).</p><p><strong>Conclusion: </strong>Finerenone appears to decrease the risk related to HF occurrence and progression, particularly in patients with CKD and diabetes, but its impact on overall mortality remains uncertain. The potential benefits need to be balanced against the risk of adverse effects. Further research is essential to explore optimal dosing and treatment duration.</p>","PeriodicalId":12491,"journal":{"name":"Frontiers in Pharmacology","volume":"16 ","pages":"1575307"},"PeriodicalIF":4.8,"publicationDate":"2025-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12464492/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145185402","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":"Role of N6-Methyladenosine (m6A) epitranscriptomic mark in regulating viral infections and target for antiviral development.","authors":"Mahmoud Bayoumi, Vidya Manju, Luis Martinez-Sobrido, Muhammad Munir","doi":"10.3389/fphar.2025.1667283","DOIUrl":"10.3389/fphar.2025.1667283","url":null,"abstract":"<p><p>Viral infectious diseases continue to pose significant public health threats, driving severe epidemics and occasional pandemics of great consequences to humans. Viral infections trigger a range of transcriptional and epitranscriptional changes, including N6-methyladenosine (m6A) modification-one of the most abundant and dynamic RNA methylation marks. Although m6A mark was identified decades ago, its functional relevance in viral RNA remained elusive until recent advances in sequencing technologies. Viruses, like their host cells, depend on mRNA for protein synthesis and must rapidly replicate and evade host immune responses. This review focuses on the critical role of m6A in the regulation of viral infections and immune responses. Herein, we explore the most recent advances on how viruses exploit the m6A marks and host m6A machinery to enhance their replication and how host m6A modifications can influence viral pathogenicity. Understanding the interplay between m6A modifications and viral life cycles will be important for the potential of targeting m6A regulatory proteins as novel antiviral strategies to control viral infections. Moreover, a better understanding of these mechanisms will contribute to deeper insights into the host innate immune response and the development of innovative antiviral therapeutics.</p>","PeriodicalId":12491,"journal":{"name":"Frontiers in Pharmacology","volume":"16 ","pages":"1667283"},"PeriodicalIF":4.8,"publicationDate":"2025-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12463980/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145185403","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":"Breaking the bottlenecks in anti-tumor angiogenic therapy: targeting vasculogenic mimicry with natural products and traditional Chinese medicine.","authors":"Huan Liu, Yuan Zhang, Xuanyu Lv, Xueying Ding, Wenlu Liao, Weifang Sun, Yanan Zhang, Chunyan Song, Yong Tang","doi":"10.3389/fphar.2025.1668083","DOIUrl":"10.3389/fphar.2025.1668083","url":null,"abstract":"<p><p>Cancer, as a major public health problem threatening human health, poses significant challenges in clinical management due to its high invasiveness, metastatic potential, and therapeutic resistance. Vasculogenic mimicry (VM) is a vascular-like structure autonomously formed by highly plastic tumor cells and has been shown to be one of the significant factors influencing the progression, metastasis, and therapeutic resistance of malignant tumors. Unlike conventional anti-angiogenic therapies that primarily target endothelial cell-mediated neovascularization, VM can facilitate the transport of oxygen and nutrients in the absence of endothelial cell participation. This unique mechanism limits the efficacy of current anti-angiogenic strategies and contributes to treatment failure and tumor recurrence. Consequently, the development of novel therapeutic strategies is of paramount importance. In recent years, accumulating evidence has demonstrated that natural products (NPs) and traditional Chinese medicine (TCM), owing to their multi-component and multi-target properties, exhibit unique advantages and significant potential in inhibiting VM formation. This review systematically summarizes recent advances in the application of NPs and TCM to inhibit VM, with a focus on their key mechanisms of action in regulating cell adhesion molecules, extracellular matrix remodeling, epithelial-mesenchymal transition, cancer stemness, hypoxia adaptation, and ferroptosis. Furthermore, we summarize the anti-VM mechanisms of NPs and TCM in multiple malignant tumors such as lung cancer, liver cancer, breast cancer, and glioblastoma, and clarify their potential application prospects. These findings provide a theoretical foundation for developing VM-targeted therapies and promote the transformation and application of NPs and TCM in the field of anti-tumor VM.</p>","PeriodicalId":12491,"journal":{"name":"Frontiers in Pharmacology","volume":"16 ","pages":"1668083"},"PeriodicalIF":4.8,"publicationDate":"2025-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12464493/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145185362","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":"A novel cytotoxic anti-B7-H3 affibody with therapeutic potential in acute myeloid leukemia.","authors":"Andrei-Mihai Vasilescu, Adina-Gabriela Vasilescu, Livia Elena Sima, Cristian V A Munteanu, Natalia Baran, Ștefan-Eugen Szedlacsek","doi":"10.3389/fphar.2025.1684226","DOIUrl":"10.3389/fphar.2025.1684226","url":null,"abstract":"<p><strong>Introduction: </strong>Acute Myeloid Leukemia (AML) is a group of very aggressive hematological malignancies, with dismal long-term survival rates and little therapeutic recourse presently. The transmembrane ligand B7-H3 is a known therapeutic target, biomarker of response and correlated with an unfavorable prognosis in several malignancies, including AML, due to acquired resistance to immune checkpoint-targeting therapies. Therefore, developing therapeutic strategies with improved efficacy to overcome this obstacle constitutes an unmet need. Our study entails the design, production and <i>in vitro</i> testing of a novel recombinant Affibody with high affinity for B7-H3 coupled with the cytotoxic peptide Magainin-2, known for its membranolytic properties and potent antimicrobial and antitumor activity.</p><p><strong>Methods: </strong>We expressed the conjugate in <i>Escherichia coli</i>, affinity purified it and confirmed its sequence by nanoLC-MS/MS. B7-H3-positive AML representative THP-1 cells and B7-H3-negative B-lymphoblastic RAJI cells were used for the experiments. The IC₅₀ of the cytotoxic conjugate was determined through MTS assay and its necrotic, apoptotic and antiproliferative activities were evaluated by flow cytometry and Western blot.</p><p><strong>Results: </strong>Overall, the results show that our cytotoxic anti-B7-H3 affibody possesses strong antiproliferative and cell death-inducing activity that is highly specific to B7-H3-expressing AML cells (IC₅₀ against THP-1 cells was 26.35 µM). Moreover, this observed activity of our conjugate is significantly more potent than the previously described activity of Magainin-2 alone.</p><p><strong>Conclusion: </strong>In conclusion, we designed, produced and evaluated a novel anti-B7-H3 cytotoxic affibody-drug conjugate (AfDC) that, from these preliminary <i>in vitro</i> data, shows high potential for translation to the therapy of AML, warranting further preclinical and translational exploration, including pharmacokinetic and <i>in vivo</i> efficacy studies.</p>","PeriodicalId":12491,"journal":{"name":"Frontiers in Pharmacology","volume":"16 ","pages":"1684226"},"PeriodicalIF":4.8,"publicationDate":"2025-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12464454/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145185233","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":"Mesenchymal stromal cell-laden hydrogels in tissue regeneration: insights from preclinical and clinical research.","authors":"Silvia Barbon, Senthilkumar Rajendran, Antara Banerjee, Pier Paolo Parnigotto, Raffaele De Caro, Veronica Macchi, Andrea Porzionato","doi":"10.3389/fphar.2025.1670649","DOIUrl":"10.3389/fphar.2025.1670649","url":null,"abstract":"<p><p>Hydrogel-based delivery systems have emerged as a promising strategy to enhance the therapeutic efficacy of mesenchymal stromal cells (MSCs) in regenerative medicine. These biomimetic platforms provide a three-dimensional microenvironment that recapitulates key features of native extracellular matrix, supporting MSC viability, retention, and function upon transplantation. Beyond acting as passive carriers, hydrogels can be engineered with tunable biochemical and mechanical properties to modulate MSC behavior, including their differentiation potential, immunomodulatory activity, and paracrine signaling. Recent advances include the development of \"smart\" hydrogels responsive to physiological stimuli, enabling controlled release of encapsulated cells or bioactive molecules in response to local cues. Preclinical studies have demonstrated enhanced tissue repair in diverse pathological contexts, including musculoskeletal, cardiovascular, gastrointestinal, dermal, and neural injuries. Importantly, translation to clinical settings is being facilitated by the use of xeno-free, good manufacturing practices (GMP)-compliant components such as platelet derivatives and synthetic polymers. Selected early-phase clinical trials support the feasibility, safety, and therapeutic potential of MSC-laden hydrogels, although further studies are required to optimize delivery parameters and regulatory compliance. This review summarizes current progress in hydrogel-MSC systems across application areas, emphasizing design principles, preclinical outcomes, and translational challenges, with the aim of guiding future developments in stem cell-based tissue regeneration.</p>","PeriodicalId":12491,"journal":{"name":"Frontiers in Pharmacology","volume":"16 ","pages":"1670649"},"PeriodicalIF":4.8,"publicationDate":"2025-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12464487/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145185241","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":"Trastuzumab Deruxtecan for brain metastatic squamous lung carcinoma with immune-related hypophysitis: a case report.","authors":"Rui Xu, Jiadi Gan, Jiarui Zhang, Linhui Yang, Yi Liu, Weimin Li, Kaige Wang, Dan Liu","doi":"10.3389/fphar.2025.1608589","DOIUrl":"10.3389/fphar.2025.1608589","url":null,"abstract":"<p><p>Immunotherapy is an important part of the first-line treatment for lung squamous cell carcinoma (LUSC) in the current guidelines. However, in case when patients experience immunotherapy-related adverse reactions, immunotherapy may be discontinued. Antibody-drug conjugates (ADCs) may be an alternative treatment if the patient harbors actionable mutations. Herein, we present a case of brain metastatic LUSC harboring <i>HER2</i> mutation who experienced hypophysitis after immunotherapy. This patient benefited from Trastuzumab Deruxtecan (T-DXd) after discontinuing immunotherapy. Therefore, T-DXd may be an alternative treatment option for LUSC patients with <i>HER2</i> mutation who are unable to continue immunotherapy.</p>","PeriodicalId":12491,"journal":{"name":"Frontiers in Pharmacology","volume":"16 ","pages":"1608589"},"PeriodicalIF":4.8,"publicationDate":"2025-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12461255/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145185359","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 how levetiracetam mitigates toxicity and ameliorates memory impairment.","authors":"Ahmad H Alhowail, Abeer M Alharbi","doi":"10.3389/fphar.2025.1651414","DOIUrl":"10.3389/fphar.2025.1651414","url":null,"abstract":"<p><p>Cognitive impairment encompasses a spectrum of deficits that markedly affect daily functioning and quality of life. Understanding the specific cognitive domains involved is thus crucial for developing targeted interventions and effective support strategies. This impairment ranges from mild cognitive decline to severe dementia and disproportionately affects older adults and cancer survivors. Multiple pathophysiological mechanisms, including elevated neuroinflammation, oxidative stress, disrupted synaptic plasticity, and neuronal apoptosis, contribute to the onset and progression of cognitive dysfunction. Emerging clinical and experimental data suggest that pharmacological interventions, including levetiracetam (LEV), a second-generation antiepileptic drug, can attenuate cognitive impairment. The neuroprotective potential of LEV is attributed to its unique mechanism of action, which involves selective binding to synaptic vesicle protein 2A and modulation of neurotransmitter release. In addition to its well-established antiepileptic effects, LEV exhibits anti-inflammatory and antioxidant properties, suggesting broader therapeutic applications in mitigating cognitive decline. This review synthesizes current knowledge on the mechanisms underlying cognitive impairment, evaluates existing measurement and prevention approaches, along with their limitations, and critically examines the potential efficacy of LEV in this context. The novelty of this review lies in its integrative focus on the mechanistic pathways through which LEV may protect against cognitive decline, with attention to conflicting findings and unresolved questions. In conclusion, current evidence suggests that LEV is a promising therapeutic candidate beyond epilepsy, though further clinical studies are needed to confirm its efficacy.</p>","PeriodicalId":12491,"journal":{"name":"Frontiers in Pharmacology","volume":"16 ","pages":"1651414"},"PeriodicalIF":4.8,"publicationDate":"2025-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12460228/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145185420","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":"Occupational toxic encephalopathy due to 1,2-dichloroethane exposure: a case series.","authors":"Tongyao Li, Wensi Hu, Xia Rong, Ping Yang, Yu Du, Songbai He, Haibo Tang, Linna Luo, Lin Shi, Junzhao Liu","doi":"10.3389/fphar.2025.1542156","DOIUrl":"10.3389/fphar.2025.1542156","url":null,"abstract":"<p><p>1,2-Dichloroethane (1,2-DCE) is a commonly used organic solvent in industrial settings. In pharmacokinetic studies using electrochemical techniques, it is widely used as an organic solvent for dissolving drugs and forms a water/1,2-DCE interface. The 1,2-DCE exposure caused by inadequate protection poses a risk of toxicity via inhalation or dermal contact. This case series documents five instances of poisoning resulting from occupational exposure to industrial products containing 1,2-DCE. 1,2-DCE can induce neurological damage, particularly affecting the central nervous system, manifesting as toxic encephalopathy. Clinical manifestations encompass headache, limb convulsions, and coma, often accompanied by increased intracranial pressure. Magnetic resonance imaging aids in the early detection of toxic encephalopathy by revealing extensive cerebral edema and diffuse, symmetrical abnormalities in signal intensity within the bilateral cerebral white matter, basal ganglia, and dentate nucleus. The principal therapeutic strategies encompass the administration of dehydrating agents, glucocorticoids, and hyperbaric oxygen therapy. Patients with mild poisoning can achieve recovery, whereas those with severe poisoning may experience fatal outcomes. Consequently, effective preventative measures must be instituted to minimize exposure to 1,2-DCE in the workplace.</p>","PeriodicalId":12491,"journal":{"name":"Frontiers in Pharmacology","volume":"16 ","pages":"1542156"},"PeriodicalIF":4.8,"publicationDate":"2025-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12461153/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145185255","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":"Improved myocardial mitochondrial energy metabolism in rats with chronic heart failure by modifying fatty acid oxidation using an extract of sand-fired aconite (Jianchang gang processing).","authors":"Hongtao Zhang, Yi Huang, Songhong Yang, Feipeng Gong, Yuncheng Gu, Qin Xie, Yanrong Ye, Xingmei Lu, Lingyun Zhong","doi":"10.3389/fphar.2025.1600410","DOIUrl":"10.3389/fphar.2025.1600410","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Introduction: &lt;/strong&gt;Sand-fired aconite slices (SFAS) demonstrate anti-heart failure effects, but the mechanism remains unclear. This study investigated myocardial mitochondrial energy metabolism as a therapeutic mechanism of SFAS in doxorubicin-induced chronic heart failure (CHF) rats.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;The CHF rat model was established via the intraperitoneal injection of doxorubicin (DOX). Following successful model production, rats were randomly assigned to nine groups. After drug administration, their cardiac function was assessed, and their cardiac tissue morphology and myocardial mitochondria were examined. Atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), norepinephrine (NE), malondialdehyde (MDA), superoxide dismutase (SOD), free fatty acid (FFA), sodium-potassium-ATPase (Na&lt;sup&gt;+&lt;/sup&gt;-k&lt;sup&gt;+&lt;/sup&gt;-ATPase), calcium-magnesium-ATPase (Ca&lt;sup&gt;2+&lt;/sup&gt;-Mg&lt;sup&gt;2+&lt;/sup&gt;-ATPase), and adenosine triphosphate (ATP) levels were quantified using enzyme-linked immunosorbent assays (ELISAs). Fatty acid translocase (CD36), carnitine palmitoyl transferase 1 (CPT1), adenosine 5'-monophosphate-activated protein kinase (AMPK), phosphorylated adenosine monophosphate-activated protein kinase (p-AMPK), peroxisome proliferator-activated receptor γ coactivator 1 alpha (PGC-1α), and Sirtuin 3 (SIRT3) protein expression levels were assessed by Western blot.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;SFAS significantly improved cardiac function in CHF rats. It increased the left ventricular ejection fraction (LVEF) (from 34.22% ± 2.03%-83.68% ± 2.34%; &lt;i&gt;P&lt;/i&gt; &lt; 0.001) and left ventricular shortening fraction (LVFS) (from 17.06% ± 1.08%-53.86% ± 2.82%; &lt;i&gt;P&lt;/i&gt; &lt; 0.001) and decreased ANP (from 551.29 ± 14.63 pg/mL to 291.96 ± 11.28 pg/mL; &lt;i&gt;P&lt;/i&gt; &lt; 0.05), BNP (from 743.15 ± 18.03 pg/mL to 478.75 ± 10.57 pg/mL; &lt;i&gt;P&lt;/i&gt; &lt; 0.001), and NE levels (from 1,105.36 ± 21.79 pg/mL to 672.67 ± 6.70 pg/mL; &lt;i&gt;P&lt;/i&gt; &lt; 0.001). Additionally, it decreased MDA production (from 8.89 ± 0.36 nmol/mL to 5.11 ± 0.35 nmol/mL; &lt;i&gt;P&lt;/i&gt; &lt; 0.05) and increased SOD activity (from 264.82 ± 4.26 pg/mL to 529.64 ± 10.27 pg/mL; &lt;i&gt;P&lt;/i&gt; &lt; 0.001), Na&lt;sup&gt;+&lt;/sup&gt;-K&lt;sup&gt;+&lt;/sup&gt;-ATPase levels (from 7.19 ± 0.65 μmol/mL to 14.08 ± 0.28 μmol/mL; &lt;i&gt;P&lt;/i&gt; &lt; 0.001), Ca&lt;sup&gt;2+&lt;/sup&gt;-Mg&lt;sup&gt;2+&lt;/sup&gt;-ATPase levels (from 0.86 ± 0.03 μmol/mL to 1.40 ± 0.02 μmol/mL; &lt;i&gt;P&lt;/i&gt; &lt; 0.05), CD36 levels (&lt;i&gt;P&lt;/i&gt; &lt; 0.05), and CPT1 levels (&lt;i&gt;P&lt;/i&gt; &lt; 0.01). Moreover, it improved mitochondrial structural damage and reduced the level of oxidative stress in cardiomyocytes. Furthermore, SFAS promoted FFA oxidation (from 1,477.49 ± 7.60 μmol/mL to 768.87 ± 82.53 μmol/mL; &lt;i&gt;P&lt;/i&gt; &lt; 0.05) and ATP production (from 2,869.85 ± 298.26 nmol/mL to 5,483.17 ± 120.03 nmol/mL; &lt;i&gt;P&lt;/i&gt; &lt; 0.001) and increased p-AMPK, PGC-1α, and SIRT3 levels (&lt;i&gt;P&lt;/i&gt; &lt; 0.05 and &lt;i&gt;P&lt;/i&gt; &lt; 0.01).&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusion: &lt;/strong&gt;By activating the AMPK/PGC-1α/SIRT3 signaling pathway, SFAS ameliorated the impaired f","PeriodicalId":12491,"journal":{"name":"Frontiers in Pharmacology","volume":"16 ","pages":"1600410"},"PeriodicalIF":4.8,"publicationDate":"2025-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12461213/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145185308","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":"The WHO's critical bacteria list: scientific response eight years after its implementation and development of an AI-based tool for its monitoring.","authors":"Juan Eduardo Robledo Almonacid, Christian Lombardo, Mariana Romano, Agustina Quiroga, Paula Cambuli Bianchi, Mauricio Hualpa, Constanza Giai, Xiomara María A Oviedo, Ramiro Alejo Salgado Mansur, Mariana Guadalupe Vallejo, Cristián Andrés Quintero","doi":"10.3389/fphar.2025.1633382","DOIUrl":"10.3389/fphar.2025.1633382","url":null,"abstract":"<p><strong>Background: </strong>In 2017, the World Health Organization (WHO) issued a global alert identifying 12 bacteria in urgent need of new treatments.</p><p><strong>Main body: </strong>This study assesses the scientific community's response to this alert by analyzing original research publications using LLMzCor, an AI-based tool developed and validated by our group. To compare trends, we focused on publications from 5 years before and after the alert, specifically on three bacteria listed in the WHO alert, sorted by priority level: <i>Acinetobacter baumannii</i> (Critical), <i>Shigella</i> spp (High), and <i>Neisseria gonorrhoeae</i> (Medium) and three non-listed as controls (<i>Rickettsia</i> spp., <i>C. trachomatis</i>, and <i>C. difficile)</i>. Articles were classified into three categories: (i) identification of Resistant strains, (ii) development of New treatments, and (iii) Immunization strategies.</p><p><strong>Results: </strong>Although overall publications increased after the WHO alert, no statistically significant changes were found in the reports of Resistant strains over time. The development of New treatments for the listed bacteria showed a slight increase, between 2% and 10%. Furthermore, Immunization strategies remained relatively unchanged, with less than 2%. Meanwhile, LLMzCor demonstrated robust performance across categories, F1-scores ranging from 0.65 to 0.72 in key classifications, while recall peaked at 0.75, indicating a high capacity to identify relevant articles. These results support the model's reliability for large-scale automated classification of scientific abstracts.</p><p><strong>Conclusion: </strong>These findings, supported by LLMzCor, underscore the urgency of a stronger WHO alert and action plans to develop new strategies against bacterial resistance.</p>","PeriodicalId":12491,"journal":{"name":"Frontiers in Pharmacology","volume":"16 ","pages":"1633382"},"PeriodicalIF":4.8,"publicationDate":"2025-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12461225/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145185417","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}