Naunyn-Schmiedeberg's archives of pharmacology最新文献

{"title":"Combined antibacterial and antibiofilm activity of an Ag-CeO₂/MgAl-LDH nanocomposite-nanoemulsion formulation against multidrug-resistant Enterococcus faecium.","authors":"Praveen Rajendra Babu, Keerthana Vedhantham, Karthikeyan Ramalingam","doi":"10.1007/s00210-026-06000-6","DOIUrl":"https://doi.org/10.1007/s00210-026-06000-6","url":null,"abstract":"<p><p>The increasing prevalence of multidrug-resistant (MDR) Enterococcus faecium has created an urgent need for alternative antimicrobial strategies capable of overcoming conventional antibiotic resistance and inhibiting biofilm formation. In the present study, the antibacterial and antibiofilm activities of an Ag-CeO₂/MgAl-LDH nanocomposite, a sunflower oil-based nanoemulsion, and their combined formulation were evaluated against both a clinical MDR isolate and the reference strain E. faecium MCC 2763. The prepared formulations were characterized using dynamic light scattering (DLS), zeta potential analysis, and Fourier transform infrared (FTIR) spectroscopy. Antibacterial activity was assessed by minimum inhibitory concentration (MIC), minimum bactericidal concentration (MBC), time-kill kinetics, impedance-based growth monitoring, bacterial adherence assays, and biofilm inhibition studies. The combined nanocomposite-nanoemulsion formulation showed greater antibacterial and antibiofilm activity than the individual formulations under the experimental conditions evaluated. Time-kill and biofilm assays indicated improved inhibition of bacterial growth and biofilm formation, while impedance measurements further supported the antibacterial activity of the combined formulation. Although the present findings demonstrate the promising antibacterial potential of the developed formulation, formal synergy analysis, cytotoxicity evaluation, advanced physicochemical characterization, and mechanistic investigations were beyond the scope of this study. These investigations will be essential in future work to further evaluate the therapeutic potential of this formulation. Overall, the developed Ag-CeO₂/MgAl-LDH nanocomposite-nanoemulsion formulation represents a promising antibacterial platform for combating multidrug-resistant Enterococcus faecium and warrants further investigation through comprehensive preclinical evaluation.</p>","PeriodicalId":18876,"journal":{"name":"Naunyn-Schmiedeberg's archives of pharmacology","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2026-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149207344","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Nanocarriers in psychiatry: a comprehensive review of emerging frontiers in the management of psychiatric disorders.","authors":"Rodayna Atef Shalaby, Omaima Naim El Gazayerly, Mohammed Abdallah Ahmed, Michael Magdy Farag, Nevine Shawky AbdelMalak","doi":"10.1007/s00210-026-05940-3","DOIUrl":"https://doi.org/10.1007/s00210-026-05940-3","url":null,"abstract":"<p><p>Psychiatric disorders are characterized by clinically significant disturbances in cognition, emotional regulation, and behavior and represent a substantial global health burden. Pharmacological management relies primarily on antidepressants, anxiolytics, antipsychotics, mood stabilizers, hypnotics, and stimulants. However, conventional therapy may be limited by unfavorable physicochemical properties, variable pharmacokinetics, suboptimal brain exposure, frequent dosing, and systemic adverse effects, which may compromise therapeutic outcomes and long-term treatment adherence. Nanocarrier-based drug delivery systems have emerged as a promising approach to address some of these limitations. By optimizing particle size, composition, morphology, and surface characteristics, nanocarriers may improve drug solubility and stability, modify pharmacokinetic and release profiles, protect therapeutic agents from degradation, and facilitate brain delivery through the blood-brain barrier-associated transport mechanisms or nose-to-brain pathways. Controlled or sustained release may additionally reduce dosing frequency and improve patients' compliance. This review critically examines organic, inorganic, and hybrid nanocarrier systems investigated for psychotropic drug delivery, with particular emphasis on brain delivery mechanisms, safety considerations, clinical translation, regulatory challenges, and emerging strategies for psychiatric nanomedicine.</p>","PeriodicalId":18876,"journal":{"name":"Naunyn-Schmiedeberg's archives of pharmacology","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2026-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149182810","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Investigating potential prognostic genes and candidate therapeutic targets for acute myeloid leukemia in food-medicine homologous plants via integrated network pharmacology and transcriptomics.","authors":"Mingxia Tang, Tao Chen, Tao Huang, Shanshan Bai, Yajiang Wang, Yanling Zhang, Lian Yan, Xia He","doi":"10.1007/s00210-026-05933-2","DOIUrl":"https://doi.org/10.1007/s00210-026-05933-2","url":null,"abstract":"&lt;p&gt;&lt;p&gt;Acute myeloid leukemia (AML) is a hematologic malignancy. Conventional chemotherapy often causes substantial adverse effects, while food-medicine homologous plants with favorable safety profiles and multitarget regulatory activities offer a promising strategy for AML treatment. This study aimed to screen core bioactive compounds from 106 food-medicine homologous plants, identify potential prognostic genes related to AML, and explore the molecular mechanisms of their anti-AML activities. Public omics cohorts for AML were systematically analyzed to screen differentially expressed genes (DEGs). The DEGs were intersected with the target genes of 106 food-medicine homologous plants to obtain candidate genes for subsequent GO/KEGG functional enrichment analysis and PPI network analysis. Core bioactive compounds were screened and prioritized via the Graph-based Bilinear Attention Network (GraphBAN) combined with druggability and toxicology screening criteria. Potential prognostic genes were identified via univariate Cox proportional hazards regression analysis and further screening. Immune infiltration analysis and gene set enrichment analysis (GSEA) were performed on the identified potential prognostic genes. Bioinformatic prediction was conducted to identify upstream transcription factors (TFs) and microRNAs (miRNAs) targeting these genes and to analyze their chromosomal distribution and subcellular localization characteristics. Binding affinity and stability between core active compounds and proteins encoded by potential prognostic genes were systematically confirmed by molecular docking and molecular dynamics simulation analyses. The expression levels of potential prognostic genes were finally validated via reverse transcription quantitative polymerase chain reaction (RT-qPCR). We identified 1102 candidate genes, 542 core bioactive compounds, and 6 potential prognostic genes. The constructed prognostic model demonstrated moderate predictive performance. Immune infiltration analysis identified 18 types of differentially infiltrated immune-cell populations (P &lt; 0.05), and GSEA results indicated that immunity-related signaling pathways were enriched in the AML high-risk subgroup. Moreover, 138 chemotherapeutic agents were identified. MYB-centered transcription factors and numerous microRNAs were found to regulate these potential prognostic genes. The genes reside on distinct chromosomes; for example, ITGB3 is located on chromosome 17. Further subcellular localization analysis revealed distinct protein distribution patterns. IGF1R, ITGB3, and SLC38A1 are predominantly located on the cell membrane, while KYNU, PDE4A, and GSTM2 are mostly located in the cytoplasm. Molecular docking revealed that the binding energy between IGF1R and MOL008397 was - 10.7 kcal/mol. Molecular dynamics simulation further confirmed the stability of this molecular complex. RT-qPCR verified distinct expression of the six prognostic genes in clinical AML blood samples. This ","PeriodicalId":18876,"journal":{"name":"Naunyn-Schmiedeberg's archives of pharmacology","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2026-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149182559","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Design and optimization of naringenin-loaded organogels for topical management of bacterial infections.","authors":"Someshwar Mankar, Kajal Madhe, Suhas Siddheshwar, Vaibhav Andhale, Achal Andhale","doi":"10.1007/s00210-026-05999-y","DOIUrl":"https://doi.org/10.1007/s00210-026-05999-y","url":null,"abstract":"<p><p>Bacterial skin infections are increasingly complicated by antimicrobial resistance, and naringenin, a citrus flavanone with membrane disrupting antibacterial activity, is limited in topical use by poor aqueous solubility and low dermal penetration. The present work was undertaken to develop and optimize naringenin loaded organogels for topical antibacterial application using a systematic quality by design approach. Naringenin loaded organogels were prepared by the hot emulsification technique and optimized through a 3² full factorial design in which glyceryl monostearate (10 to 20% w/w) and Capryol™ PGMC (5 to 15% w/w) concentrations were varied. The formulations were characterized for gel strength, viscosity, spreadability, drug content, drug excipient compatibility by FTIR, in vitro drug release, release kinetics, antibacterial activity and accelerated stability. The pH values (6.12 to 6.42) were suitable for topical application and the drug content was high (96.8 to 99.1%). Gel strength (42.6 to 92.2 g) and viscosity (3842.6 to 9922.3 cps) increased with glyceryl monostearate concentration, whereas spreadability (16.5 to 29.6 g · cm/s) decreased. Response surface methodology identified MF5, containing 15% w/w glyceryl monostearate and 10% w/w Capryol™ PGMC, as the optimized formulation, with experimental values for gel strength (78.5 g), viscosity (6082.4 cps) and drug release at 12 h (89.74%) closely matching the predicted values (relative error below 2.5%). The optimized formulation followed zero order release kinetics (R² = 0.9859) with a non Fickian diffusion mechanism (n = 0.79), retained antibacterial activity against Escherichia coli and Staphylococcus aureus, and remained stable under accelerated conditions for three months. Optimized naringenin loaded organogel exhibited favorable physiochemical properties with an sustained in-vitro drug release and antibacterial activity against Escherichia coli and Staphylococcus aureus. The optimized formulation showed reduced antibacterial activity under the same experimental conditions when compared with the standard ciprofloxacin, and showed to release the antibiotic continuously from the organogel matrix. By using the factorial design approach, an optimized formulation having reproducible quality attributes and acceptable physicochemical stability after accelerated storage was achieved.</p>","PeriodicalId":18876,"journal":{"name":"Naunyn-Schmiedeberg's archives of pharmacology","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2026-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149182383","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Amantadine attenuates LPS-associated acute hepatic injury through anti-inflammatory and antiapoptotic responses: potential involvement of TXNIP/NLRP3-related signaling.","authors":"Girayhan Celik, Halil Asci, Serife Tasan, Simge Garli, Muhammet Yusuf Tepebasi, Ilter Ilhan, Abdurrahman Gulal, Ozlem Ozmen","doi":"10.1007/s00210-026-06001-5","DOIUrl":"https://doi.org/10.1007/s00210-026-06001-5","url":null,"abstract":"<p><p>The hepatoprotective potential of amantadine (AMN) against lipopolysaccharide (LPS)-triggered hepatic injury was investigated by evaluating inflammation, inflammasome activation, and apoptosis-related signaling pathways. The study consists of four groups: Control, LPS, LPS + AMN, and AMN. Histopathological changes were evaluated in hematoxylin and eosin-stained liver sections. Immunohistochemical analyses were performed to assess C-reactive protein (CRP), serum amyloid A (SAA), and tumor necrosis factor-alpha (TNF-α). Serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) activities were measured as biochemical indicators of liver injury. Interleukin-1 beta (IL-1β), interleukin-18 (IL-18), NLR family pyrin domain containing 3 (NLRP3), thioredoxin-interacting protein (TXNIP), and Bcl-2-associated X protein (BAX) gene expression was determined liver tissue. LPS administration caused severe histopathological damage, inflammatory cell infiltration, and significant elevations in AST and ALT activities. Increased immunoreactivity of CRP, SAA, and TNF-α, together with upregulated IL-1β, IL-18, NLRP3, TXNIP, and BAX expression, indicated enhanced inflammatory and apoptotic responses. Administration of AMN was associated with attenuation of tissue damage, accompanied by lower inflammatory marker levels, decreased serum transaminase activities, and altered expression of key genes related to inflammasome activation and apoptotic pathways. No significant differences were detected between the LPS + AMN groups and controls groups. The present findings are consistent with an association between AMN administration and attenuation of LPS-associated hepatic injury, accompanied by changes in inflammatory responses, inflammasome-related signaling, and apoptosis-related pathways. These findings are consistent with a potential hepatoprotective effect of AMN in inflammation-associated liver injury and warrant further investigation.</p>","PeriodicalId":18876,"journal":{"name":"Naunyn-Schmiedeberg's archives of pharmacology","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2026-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149183260","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Bacillus-based probiotics ameliorate bleomycin-induced pulmonary fibrosis in rats: coupling intestinal barrier reinforcement to the modulation of M2 macrophage polarization/TGF-β/p38MAPK and inflammasome-driven pyroptosis.","authors":"Noha F Hassan, Samah G Ahmed, Hassan Aboul-Ella, Maha A Salem, Asmaa Gohar, Asmaa M El-Maghraby, Dalia M Hamed, Marwa A Essa, Enas S Gad","doi":"10.1007/s00210-026-05988-1","DOIUrl":"https://doi.org/10.1007/s00210-026-05988-1","url":null,"abstract":"<p><p>Pulmonary fibrosis (PF) is a chronic, progressive lung disorder with an 87.5% mortality rate recorded in aged patients. Emerging evidence bridges gut dysbiosis to PF pathogenesis. The consumption of a Bacillus-based probiotic exhibited immunomodulatory and anti-inflammatory effects by alleviating gut dysbiosis and restoring gut microbiome composition, positioning it as a promising therapeutic strategy for gut-organ axis disorders. The present study investigated the therapeutic effects of Bacillus-based probiotics in a rat model of PF by targeting the gut-lung axis. Rats were randomly assigned to five groups: Group I (the normal control group) and Group II received a single intratracheal instillation of bleomycin (BLM) (5 mg/kg). All treated groups received BLM and commenced treatment fourteen days later. Group III: received B. clausii. Group IV: received B. coagulans. Group V: received a combination of both strains. In vitro and in vivo analyses showed that the probiotic strains exhibited gut survivability, colonization associated with restoration of intestinal barrier integrity, and an SCFA profile. The dual therapy exerted a notable immunomodulatory effect by suppressing pulmonary M2 macrophage polarization (CD206 and Arg1), inhibiting the TGF-β/p38MAPK-JNK/NF-κB signaling cascade, mitigating inflammatory and fibrotic responses, and diminishing NLRP3/Caspase-1/IL-1β/GSDMD-N-mediated pyroptosis, thereby disrupting the vicious cycle of inflammation and fibrogenesis. Interplay with the Nrf2 axis activates antioxidant defense. This study resolves this knowledge gap by investigating the therapeutic potential of Bacillus-based probiotics to alleviate PF by modulating the gut-lung axis, offering an innovative platform for the treatment of PF that extends beyond current Lactobacillus-focused research.</p>","PeriodicalId":18876,"journal":{"name":"Naunyn-Schmiedeberg's archives of pharmacology","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2026-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149182056","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Combined rituximab and magnesium acetyl taurate therapy attenuates neurodegeneration via ERK/c-JNK/P38MAPK signaling modulation in methylmercury-induced amyotrophic lateral sclerosis-like neurotoxicity.","authors":"Trina Saha, Sidharth Mehan","doi":"10.1007/s00210-026-05948-9","DOIUrl":"https://doi.org/10.1007/s00210-026-05948-9","url":null,"abstract":"<p><p>Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder characterized by motor neuron degeneration, oxidative stress, neuroinflammation, mitochondrial dysfunction, and dysregulation of intracellular signaling pathways. The present study investigated the neuroprotective potential of rituximab (RTXMB), alone and in combination with magnesium acetyl taurate (MACT600), against methylmercury (MLMC5)-induced ALS-like pathology in adult Wistar rats through modulation of the ERK/c-JNK/P38MAPK signaling pathway. ALS was induced by oral administration of MLMC5 (5 mg/kg) for 21 days. RTXMB (50 and 100 mg/kg) and MACT600 (600 mg/kg) treatments were administered from day 22 to day 42. Behavioral assessments, neurochemical estimations, ELISA, Western blotting, hematological analysis, gross morphology, and histopathological evaluations were performed. MLMC5 exposure produced significant impairments in locomotion, muscular strength, cognition, and emotional behavior, accompanied by increased oxidative stress, inflammatory cytokines, glutamate excitotoxicity, apoptotic markers, methylmercury accumulation, and dysregulation of ERK/c-JNK/P38MAPK signaling. Moreover, MLMC5 caused marked demyelination, neuronal degeneration, neurotransmitter imbalance, skeletal muscle damage, and hematological dysfunction. RTXMB treatment significantly attenuated these pathological alterations in a dose-dependent manner, with RTXMB100 showing greater neuroprotective efficacy. Combined administration of RTXMB100 and MACT600 demonstrated the most pronounced therapeutic effects by restoring antioxidant defenses, suppressing neuroinflammation and apoptosis, normalizing neurotransmitter levels, preserving myelin integrity, and improving neuronal morphology. The findings suggest that RTXMB, particularly in combination with MACT600, exerts potent neuroprotective effects against ALS-like pathology via modulation of MAPK signaling pathways and may represent a promising therapeutic strategy for ALS management.</p>","PeriodicalId":18876,"journal":{"name":"Naunyn-Schmiedeberg's archives of pharmacology","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2026-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149170131","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The global surge of cocaine use disorder: a 30-year burden analysis from the GBD 2021.","authors":"Zhuping Ren, Xinhui Wu, Jing Chen, Xiaoli Li","doi":"10.1007/s00210-026-05992-5","DOIUrl":"https://doi.org/10.1007/s00210-026-05992-5","url":null,"abstract":"<p><p>Cocaine use disorder (CUD) represents a growing global health challenge with an inadequately characterized epidemiological profile. Utilizing data from the Global Burden of Disease (GBD) 2021 study across 204 countries or territories (1990-2021), this study assessed age-standardized incidence (ASIR), prevalence (ASPR), mortality (ASMR), and disability-adjusted life years (DALYs) rates. Key trends were analyzed using Estimated Annual Percentage Change (EAPC). Additional analyses included frontier mapping against the Socio-demographic Index (SDI), decomposition to identify driving factors, and ARIMA modeling for future projections. Findings revealed that global cocaine production tripled between 2009 and 2023, coinciding with a rising CUD burden: ASMR increased by 114% from 1990 to 2021, with males experiencing a faster mortality increase compared to females. High-income and Latin American regions bore the highest burden-the USA led in ASIR and ASMR, while Spain saw declines after 2005 due to stringent policies. SDI strongly correlated with ASIR (ρ = 0.59), and high-SDI regions had higher DALYs than low-SDI areas. Projections indicate accelerating ASMR and DALY rates in high-income countries by 2036. CUD imposes an escalating and inequitable global burden, disproportionately affecting males, high-income populations, and the Americas. Addressing this crisis requires targeted interventions and improved surveillance of evolving use patterns and comorbidities.</p>","PeriodicalId":18876,"journal":{"name":"Naunyn-Schmiedeberg's archives of pharmacology","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2026-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149170022","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effects of vitamin B1/B6/B12 complex on methotrexate-induced hepatorenal toxicity in a short-term acute rat model.","authors":"Ayça Toprak-Semiz, Esra Deniz, Atilla Topçu, Sibel Mataracı Karakaş, Çiğdem Öztürk, Efsane Yavuz-Bedir","doi":"10.1007/s00210-026-05993-4","DOIUrl":"https://doi.org/10.1007/s00210-026-05993-4","url":null,"abstract":"<p><p>This study evaluated the effects of vitamin B1/B6/B12 complex supplementation on methotrexate (MTX)-induced hepatorenal injury in a short-term, single-dose acute rat model. Male Wistar rats were assigned to control, MTX, low-dose (MTX + VB-L), and high-dose (MTX + VB-H) vitamin B complex groups. A single MTX (20 mg/kg) was administered intraperitoneally on day 7. Vitamin B1/B6/B12 was administered intraperitoneally daily at 16/16/0.16 or 32/32/0.32 mg/kg on days 1-14. Samples were collected on day 14. Serum AST, ALT, urea, and creatinine, hepatic, and renal thiobarbituric acid reactive substances (TBARS) and total thiol (TT), and histopathological changes were evaluated. MTX significantly increased AST, urea, creatinine, hepatic and renal TBARS, and multiple histopathological scores compared with controls. Compared with MTX alone, AST and hepatic TBARS were significantly lower only in the MTX + VB-H group, whereas creatinine and renal TBARS were significantly lower in both treatment groups. Renal TBARS was significantly lower in MTX + VB-L than in MTX + VB-H. Neither the treatment group differed significantly from the MTX group in ALT, urea, TT, or any hepatic or renal histopathological parameter. Vitamin B complex co-administration was associated with improvements in selected biochemical markers and lower TBARS levels, without statistically significant histopathological improvement. The absence of a vitamin-only group limits distinction between MTX-specific attenuation and independent formulation effects. Further preclinical studies are required before clinical implications can be established.</p>","PeriodicalId":18876,"journal":{"name":"Naunyn-Schmiedeberg's archives of pharmacology","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2026-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149170496","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mapping the knowledge landscape and identifying frontiers of mitochondrial dysfunction in sepsis-associated acute kidney injury: a four-decade bibliometric and visualized analysis.","authors":"Cai-Xia Sun, Yun-Sheng Liu, Zeng-Wei Kou, Han Tang","doi":"10.1007/s00210-026-05984-5","DOIUrl":"https://doi.org/10.1007/s00210-026-05984-5","url":null,"abstract":"<p><p>Mitochondrial dysfunction has been recognized as a central pathogenic event and is under active investigation as a candidate therapeutic target in sepsis-associated acute kidney injury (SA-AKI). This study aims to employ multi-tool bibliometric analysis to systematically map the four-decade intellectual landscape of this field, thereby identifying emerging research hotspots and outlining priority-setting directions for future pharmacological investigation. Because publication and citation metrics quantify scholarly attention rather than therapeutic efficacy, the pathways highlighted here reflect research trends and priority-setting signals, not established therapeutic targets. A comprehensive literature retrieval was conducted across PubMed, Web of Science, and Scopus up to March 18, 2026. Following rigorous data cleaning, 837 publications were analyzed using CiteSpace, VOSviewer, and the bibliometrix R package to visually evaluate publication trends, knowledge networks, and evolving research hotspots. Cumulative publication output exhibits sustained exponential growth (R² = 0.997), accelerating significantly post-2010. China and the USA dominate global productivity, though institutional collaboration networks reveal pronounced regional clustering. Notably, publication hubs have transitioned significantly from traditional critical care journals to molecular and pharmacological journals, consistent with a shifting emphasis of scholarly attention toward molecular and pharmacological research themes. Keyword and citation burst analyses suggest that the research frontier has evolved from broad physiological observations to specific subcellular executioners. Mitochondria-mediated programmed cell death (apoptosis, pyroptosis, and ferroptosis) and oxidative stress have become the most prominent bibliometric hotspots and candidate pharmacological targets. The field of SA-AKI research has shown a pronounced, publication-driven shift from clinical phenotyping to the target-driven molecular deconstruction of mitochondrial damage; we emphasize that this result reflects research priorities, not proven therapeutic efficacy of these targets. To overcome current translational bottlenecks and off-target effects of existing agents, future drug development should transition from isolated in vitro models toward clinical multi-omics validation. Developing innovative targeted delivery systems (such as engineered nanomaterials and exosomes) and multi-target synergistic therapies will need rigorous empirical testing to determine whether they can precisely mitigate the complex SA-AKI \"mitochondrial storm\".</p>","PeriodicalId":18876,"journal":{"name":"Naunyn-Schmiedeberg's archives of pharmacology","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2026-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149169965","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}