BMC Pharmacology & Toxicology最新文献

{"title":"Modeling of colchicine biotransformation by COVID-19 associated Klebsiella pneumoniae: synergistic effects of cell adaptation and gamma irradiation.","authors":"Walaa S Hendawy, Amany Badr El-Deen Abd El-Aziz, Heba Abd-Alla El-Bialy","doi":"10.1186/s40360-026-01174-4","DOIUrl":"10.1186/s40360-026-01174-4","url":null,"abstract":"<p><strong>Background: </strong>Microbial biotransformation strategies for prescribed drugs have attracted great interest because the biotransformation process simulates what happens in the human metabolism and may be considered a resource for new pharmaceuticals.</p><p><strong>Methods: </strong>The promising candidate for colchicine biotransformation was identified using Matrix-Assisted Laser Desorption Ionization Time-of-Flight (MALDI-TOF/MS). Colchicine was quantified by a modified procedure based on the reduction of alkaline potassium permanganate and HPLC. Response surface methodology (RSM) was used for optimizing and modeling colchicine biotransformation. The colchicine-metabolizing products were identified using liquid chromatography-electrospray ionization-tandem mass spectrometry.</p><p><strong>Results: </strong>Fifteen bacteria infected the upper respiratory tract during the COVID-19 pandemic were collected and screened for colchicine resistance. One of them could metabolize 41.38% colchicine in enriched SF2 medium supplemented with 7gl^- 1 colchicine and was identified as Klebsiella pneumoniae-4. The biotransformation of colchicine was optimized using RSM upon exposing K. pneumoniae-4 cells to gamma irradiation stress. The predictive model revealed the superiority of cell adaptation before the colchicine conversion process. The RSM optimizer showed the maximum colchicine biotransformation was achieved at variable levels: 0.41 kGy irradiation dose and 9.55 d incubation time. Chromatographic analysis showed a variation in the chemical composition of colchicine metabolized products.</p><p><strong>Conclusions: </strong>The main colchicine metabolized products; 3-(4-hydroxyphenyl) propanoic acid, 4'-hydroxy-2'-methylacetophenone, dihydrorotenone, and glabridin, potentially could be applied in the medical field for more functions than those described for the parent compound.</p>","PeriodicalId":9023,"journal":{"name":"BMC Pharmacology & Toxicology","volume":"27 1","pages":""},"PeriodicalIF":2.7,"publicationDate":"2026-06-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13312506/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148350526","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comparative efficacy and safety of oral ivermectin, topical permethrin, and combination in the treatment of patients with classic scabies: systematic review and network meta-analysis.","authors":"Rowena F Genuino, Ma Christina Filomena R Batac, Clarence Pio Rey C Yacapin, Belen L Dofitas, Kimberly Anne G Ednalino, Ma Isabela P Ong, Ma Bettina Teresa G Pascual, Francis R Capule, Fernando B Garcia, Mary Ann J Ladia, Malaya P Santos, Ailyn M Yabes, Amiel Nazer C Bermudez, Maria Stephanie Fay S Cagayan","doi":"10.1186/s40360-026-01171-7","DOIUrl":"10.1186/s40360-026-01171-7","url":null,"abstract":"<p><strong>Background: </strong>Oral ivermectin is commonly used as a second-line treatment for classic scabies, particularly in cases of treatment failure or poor adherence to topical permethrin, the standard of care. However, the comparative efficacy and safety of oral ivermectin, alone or in combination with permethrin, remains unclear. This systematic review and network meta-analysis evaluated the efficacy and safety of these treatments to guide clinicians and policymakers.</p><p><strong>Methods: </strong>On April 17, 2022, we conducted a comprehensive search of databases, including MEDLINE and CENTRAL, as well as secondary sources for randomized controlled trials comparing oral ivermectin, alone or in combination with topical permethrin, and topical permethrin, or any of the three with other scabicides or placebo/vehicle/no treatment among patients with classic scabies. The primary outcomes were clinical cure and serious adverse events. We assessed the risk of bias using the Cochrane Risk of Bias 2.0 and evaluated the certainty of evidence using the GRADE approach. Network meta-analyses were performed using available case analysis and a random-effects model. Sensitivity and subgroup analyses explored the impact of methodologic decisions and known effect modifiers. Effect estimates and certainty of evidence ratings were presented in the Summary of Findings tables.</p><p><strong>Results: </strong>We included 38 RCTs (N = 4879), most of which had moderate or high overall risk of bias. Oral ivermectin, given in varying dosing regimens (single dose, two-dose, or flexible dosing) showed little or no difference in clinical cure rates compared to permethrin, which was also administered in different dosing schedules, at one to two weeks post-treatment (network RR 0.95, 95% CI [0.89, 1.02]; 30 RCTs, N = 3469; global inconsistency P = 0.42; low certainty evidence). Serious adverse events were rare (1/3212; 0.03%, 95% CI [0.000079, 0.17]; 29 RCTs; very low certainty evidence). One child who received oral ivermectin was hospitalized for cellulitis but eventually recovered. Limited data (1 RCT; n = 100) suggested that combination oral ivermectin/permethrin may be as effective or more effective than permethrin for clinical cure at one to two weeks (network RR 1.21, 95% CI [0.94, 1.56]; low certainty evidence).</p><p><strong>Conclusion: </strong>There may be little or no difference between oral ivermectin and permethrin in clinical cure. However, combination therapy with oral ivermectin and permethrin may be as good as or better than permethrin alone. The rate of serious adverse events is uncertain. Further well-designed RCTs should be conducted to confirm the findings and inform clinical practice and public health policy on scabies control.</p><p><strong>Study registration: </strong>UPM RGAO-2021-1058; PHRR230322-005013; PROSPERO CRD42022278007.</p>","PeriodicalId":9023,"journal":{"name":"BMC Pharmacology & Toxicology","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2026-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13576335/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148337717","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinical characteristics and outcomes of pediatric methylphenidate intoxication: a five-year single-center study.","authors":"Pırıl Yıldız, Ali Yurtseven, Caner Turan, Burcu Vural Atalay, Eylem Ulas Saz","doi":"10.1186/s40360-026-01177-1","DOIUrl":"10.1186/s40360-026-01177-1","url":null,"abstract":"<p><strong>Background: </strong>Methylphenidate is widely prescribed for attention-deficit/hyperactivity disorder, and its use has increased substantially in recent years. Although generally considered safe within therapeutic ranges, supratherapeutic ingestion may result in various systemic adverse effects. This study aimed to evaluate the demographic and clinical characteristics of children presenting with overdose ingestion and to identify potential factors associated with symptom development.</p><p><strong>Methods: </strong>We conducted a retrospective review of patients younger than 18 years who presented to a tertiary pediatric emergency department between January 1, 2020, and December 31, 2024, due to overdose ingestion. Demographic characteristics, psychiatric history, ingested dose, mode of exposure, clinical findings, emergency department course, and factors potentially associated with adverse effects were analyzed.</p><p><strong>Results: </strong>Thirty-two patients were included; 72% were female, and ingestion was intentional in 84%. The mean ingested dose was 5.7 mg/kg. Clinical symptoms developed in 41% of patients. The most frequent findings were tachycardia (38%), mild hypertension (34%), agitation (22%), and seizures (16%). Although most cases were mild and resolved within 12 h of observation, one toddler developed neuropsychiatric manifestations requiring close monitoring with full recovery within 48 h. No statistically significant association was observed between age, sex, gastrointestinal decontamination status, or reported ingested dose and the development of clinical symptoms (p > 0.05).</p><p><strong>Conclusions: </strong>Pediatric methylphenidate intoxication is generally mild, but severe neuropsychiatric and cardiovascular effects may occur. Careful clinical monitoring remains essential.</p><p><strong>Trial registration: </strong>Not applicable.</p>","PeriodicalId":9023,"journal":{"name":"BMC Pharmacology & Toxicology","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2026-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13576354/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148337794","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Complexed rifampicin with iron mitigates doxorubicin-induced nephrotoxicity.","authors":"Omnia A Basal, Entsar A Saad, Rana R El Sadda","doi":"10.1186/s40360-026-01161-9","DOIUrl":"10.1186/s40360-026-01161-9","url":null,"abstract":"<p><strong>Background: </strong>Kidney disease represents a significant global health challenge that can lead to serious health complications. The chemotherapeutic agent 'doxorubicin' has nephrotoxic effects as an adverse effect. Ongoing research is focused on finding protective agents that can alleviate doxorubicin's adverse effects and enhance treatment results. Recently, an iron-rifampicin complex has been developed, showing promising anticancer activity with improved safety compared to a conventional drug. This study aimed to evaluate the potential protective effects of this iron-rifampicin complex, which has not been previously explored, against doxorubicin-induced nephrotoxicity in mice.</p><p><strong>Methods: </strong>Six groups of sixty male albino mice were used: Control, Nephrotoxicity (Neph), Neph+low dose of iron-rifampicin complex (0.071 mg iron-rifampicin complex/kg), Neph+high dose of iron-rifampicin complex (0.107 mg iron-rifampicin complex/kg), Complex control in high dose (0.107 mg iron-rifampicin complex/kg), and Vehicle control. The following parameters were evaluated: body weight, kidney weight, kidney index, creatinine, urea, uric acid, sodium, potassium, calcium, phosphorus, malondialdehyde, nitric oxide, reduced glutathione, catalase, superoxide dismutase, glutathione peroxidase, and vascular endothelial growth factor (VEGF), along with kidney histopathology.</p><p><strong>Results: </strong>Doxorubicin-induced nephrotoxicity led to a significant reduction (p < 0.001) in body weight, kidney weight, kidney index, antioxidants, and VEGF, while increasing (p < 0.001) minerals, malondialdehyde, nitric oxide, creatinine, urea, and uric acid, alongside worsened kidney architecture. The iron-rifampicin complex improved all these parameters (p < 0.05), moving them closer to normal levels, particularly at the lower dosage, mainly by reducing oxidative stress and preserving VEGF.</p><p><strong>Conclusion: </strong>In conclusion, we propose the iron-rifampicin complex as a potential candidate for nephroprotection against doxorubicin-induced nephrotoxicity, subject to further validation.</p>","PeriodicalId":9023,"journal":{"name":"BMC Pharmacology & Toxicology","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2026-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13296156/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148306867","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pregabalin enhances the proliferative potential of pancreatic cancer in vitro but not in mice with pancreatic cancer.","authors":"Tomoaki Itaya, Makoto Sano, Ichie Kajiwara, Yukino Oshima, Tomoya Kuramochi, Jinsuk Kim, Osamu Kitajima, Hideaki Ijichi, Takahiro Suzuki","doi":"10.1186/s40360-026-01176-2","DOIUrl":"10.1186/s40360-026-01176-2","url":null,"abstract":"<p><strong>Background: </strong>We previously reported that mirogabalin, a selective voltage-gated calcium channel α2δ1/α2δ2 ligand, increases the proliferative potential of pancreatic cancer. However, the risk of pregabalin, a non-selective α2δ ligand, is unknown in pancreatic cancer. Therefore, the proliferation of murine pancreatic cancer cell lines was studied following treatment with pregabalin.</p><p><strong>Methods: </strong>Six-week-old pancreatic cancer mouse model KPPC (LSL-Kras^G12D/+; Trp53^flox/flox; Pdx-1^cre/+) was orally administrated pregabalin 30 mg · kg^-1 · day^-1 (n = 10), or vehicle water (n = 14) until the humane endpoint (no activity, food intake of <1 g · day^-1 or more than 20% body weight loss within several days). Cancer-related pain was assessed using the scores of the hunching and mouse grimace scale. Tumor status and plasma cytokine levels were determined using histopathological analysis and cytokine antibody arrays, respectively. Proliferative effect of pregabalin was investigated using mouse pancreatic ductal adenocarcinoma cell lines.</p><p><strong>Results: </strong>The number of pancreatic cancer cells were increased by 100 and 300 μM pregabalin in vitro. The pain scores in KPPC mice were decreased by pregabalin, but there was no significant difference in the survival rate or tumor size. Interestingly, pregabalin increased the local infiltration of CD8⁺ and CD4⁺ lymphocytes, natural killer cells and CD8⁺ and CD4⁺ dendritic cells. In contrast, M2-like tumor-associated macrophages and cancer-associated fibroblasts were reduced. Similar to the results of immuno-inflammatory alterations, plasma cytokines such as tumor necrosis factor-α, interleukin (IL)-6, IL-10, IL-13, CC chemokine ligand (CCL)1, CCL2, CCL3, CCL5 and CCL17 decreased, while IL-2, IL-15, CCL19, CCL21, C-X-C motif ligand (CXCL)10, CXCL16 and XCL1 increased by pregabalin.</p><p><strong>Conclusions: </strong>These findings suggest that pregabalin increases the proliferative ability of pancreatic cancer cells in vitro without promoting tumor growth in vivo. Additionally, it induces an alteration with an increase in tumor-infiltrating lymphocytes and dendritic cells, along with a decrease in M2-like tumor-associated macrophages and cancer-associated fibroblasts in vivo.</p>","PeriodicalId":9023,"journal":{"name":"BMC Pharmacology & Toxicology","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2026-06-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13540837/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148300762","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Safety, tolerability, pharmacokinetics, and pharmacodynamics of SHR8554, a biased µ-opioid receptor agonist: a phase I trial in healthy volunteers.","authors":"Lifang Zhang, Ge Luo, Haiying Wang, Honggang Lou, Min Yan","doi":"10.1186/s40360-026-01172-6","DOIUrl":"10.1186/s40360-026-01172-6","url":null,"abstract":"<p><p>This randomized, placebo-controlled, dose-escalation phase I trial evaluated the safety, tolerability, pharmacokinetic (PK), and pharmacodynamic (PD) profiles of SHR8554, a biased µ-opioid receptor agonist, in healthy male volunteers under different infusion durations. The study included three cohorts: a randomized, double-blind, placebo-controlled single-infusion cohort (0.25-3 mg administered over 30 min), an open-label infusion-duration cohort evaluating 0.75 mg administered over 15, 5, or 2 min, and a CYP2D6 poor metabolizer cohort receiving a single 1.5 mg dose over 30 min. A total of 56 participants were enrolled. The maximum tolerated dose (MTD) of SHR8554 was 3 mg. The most common treatment-emergent adverse events (TEAEs) were dizziness, nausea, and vomiting, with higher incidence at increased doses and shorter infusion durations. PK analyses showed that systemic exposure (Cmax and AUC) increased in a slightly less than dose-proportional manner across the 0.75-3 mg dose range, with a mean elimination half-life of approximately 6 h. Infusion duration had minimal impact on overall drug exposure. A measurable analgesic effect was first observed at 1.5 mg, with onset within 10 min after administration and duration of approximately 4 h. SHR8554 increased pain tolerance and reduced numerical rating scale (NRS) scores in an exploratory cold pain model, although no clear dose-dependent trend was observed. SHR8554 was generally well tolerated within the tested dose range and demonstrated preliminary analgesic activity in healthy volunteers.</p>","PeriodicalId":9023,"journal":{"name":"BMC Pharmacology & Toxicology","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2026-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13536600/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148293336","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Bifenthrin exacerbates ulcerative colitis via immunotoxicity: network toxicology and experimental validation reveal novel therapeutic targets.","authors":"Lingxiao Wang, Weixing Zhang, Yifan Kang, Yaoping Li","doi":"10.1186/s40360-026-01173-5","DOIUrl":"10.1186/s40360-026-01173-5","url":null,"abstract":"<p><p>Bifenthrin (BF) is a widely used pyrethroid insecticide and is recognized as an endocrine-disrupting chemical (EDC). Accumulating evidence indicates that long-term exposure to BF can induce a variety of adverse health outcomes. However, its potential role in the pathogenesis of ulcerative colitis (UC) remains elusive. In this study, we integrated data from multiple databases-including the Comparative Toxicogenomics Database (CTD), TargetNet, GeneCards, SwissTargetPrediction, and STITCH-to predict potential molecular targets of BF. UC-associated genes were compiled from GeneCards, Online Mendelian Inheritance in Man (OMIM), DisGeNET, Therapeutic Target Database (TTD), and DrugBank. Candidate targets were identified by intersecting predicted BF targets with UC-related genes, followed by functional enrichment analysis using DAVID. The STRING database and Cytoscape software were employed to construct protein-protein interaction (PPI) networks and screen for hub genes. A diagnostic model based on these hub genes was established and validated using the GSE47908 and GSE13367 datasets. Additionally, immune infiltration analysis was performed to compare the UC group with controls, identifying immune cell types significantly associated with the target genes. Molecular docking simulations via AutoDock Vina were conducted to evaluate the binding affinities between BF and the five hub proteins. Functional analysis revealed that the candidate genes were primarily enriched in pathways related to oxidative stress and inflammatory responses. Five core hub genes-BCL2, TP53, TNF, IL6, and PTGS2-were consistently identified across all analytical platforms. In vitro experiments demonstrated that BF exposure significantly exacerbated colonic inflammation by downregulating anti-inflammatory/apoptotic genes (BCL2, TP53) and upregulating pro-inflammatory markers (IL6, TNF, PTGS2). Collectively, our findings suggest that bifenthrin may promote colorectal inflammation by dysregulating key genes and modulation of the pro-inflammatory immune microenvironment, thus providing novel insights into the environmental etiology of UC.</p>","PeriodicalId":9023,"journal":{"name":"BMC Pharmacology & Toxicology","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2026-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13501640/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148257213","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Analysis of in vitro profiling data of cosmetic ingredients within the Tox21 10K compound library for bioactivity and potential toxicity.","authors":"Laken Kruger, Deborah K Ngan, Tuan Xu, Menghang Xia, Stephen S Ferguson, David M Reif, Anton Simeonov, Ruili Huang","doi":"10.1186/s40360-026-01165-5","DOIUrl":"10.1186/s40360-026-01165-5","url":null,"abstract":"<p><strong>Background: </strong>Cosmetics are defined by the U.S. Food and Drug Administration (FDA) as \"articles intended to be rubbed, poured, sprinkled, or sprayed on, introduced into, or otherwise applied to the human body…for cleansing, beautifying, promoting attractiveness, or altering the appearance\". However, the safety of cosmetic ingredients is the responsibility of the manufacturer and exposure to some of these chemicals can result in unintentional harmful effects in humans. Thus, some states are banning specific chemicals, at the state legislation level, from being used in cosmetics, which includes known endocrine disruptors such as dibutyl phthalate, diethylhexyl phthalate, and per- and polyfluoroalkyl substances (PFAS). In this study, we aim to determine the toxicity pathways significantly affected by the cosmetic ingredients (both banned and non-banned), compared to the non-cosmetics compounds in the Tox21 10K library.</p><p><strong>Methods: </strong>The Tox21 10K compound library (which includes 113 banned, 927 non-banned cosmetic ingredients and 8,185 non-cosmetic compounds) was previously screened against a panel of ~ 90 cell-based and biochemical assays. The hit rates (i.e., the percentage of compounds active in an assay) of the cosmetic and non-cosmetic compounds, as well as banned and non-banned compounds, in each Tox21 assay were compared using a Fisher's exact test, and a p-value < 0.05 was considered statistically significant.</p><p><strong>Results: </strong>We found that the evaluated cosmetic compounds were significantly more active in 11 antagonist mode assays and 23 agonist mode assays compared to the non-cosmetic compounds. The banned compounds were significantly more active in 7 antagonist mode and 6 agonist mode assays compared to the non-banned compounds. The targets of the antagonist assays included enzymes such as CYP2C19 and aromatase (CYP19A1), and the agonist assays included the Keap1/Nrf2 antioxidant response element pathway.</p><p><strong>Conclusions: </strong>In the present study, we compared the bioactivity profiles of cosmetic ingredients and non-cosmetic compounds (not used in cosmetics), as well as the banned and non-banned cosmetic ingredients, across the Tox21 assays. The analyses revealed distinct molecular pathways for these chemicals which furthers our mechanistic understanding of cosmetics ingredient toxicity and may help direct the selection of cosmetic ingredients in the future with potentially less bioactivity.</p><p><strong>Clinical trial number: </strong>Not applicable.</p>","PeriodicalId":9023,"journal":{"name":"BMC Pharmacology & Toxicology","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2026-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13508416/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148263112","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Integrating machine learning and retrospective cohort to explore the effects of AEDs on the prognosis of LGG and identify related molecular targets.","authors":"Ming Zhou, Qinhong Huang, Hui Liang, Hanjie Yang, Min Li","doi":"10.1186/s40360-026-01167-3","DOIUrl":"10.1186/s40360-026-01167-3","url":null,"abstract":"<p><p>Antiepileptic drugs (AEDs) were frequently employed in glioma patients, especially those with low-grade glioma (LGG), in which epilepsy manifested in roughly 70-90% of cases. It has been reported that some AEDs can improve the survival of glioma patients. However, the molecular mechanisms of AEDs through which affect LGG prognosis remained unclear. Therefore, this study integrated 105 targets of 10 AEDs, by using machine learning, molecular docking, a retrospective clinical cohort, and in vitro experiments to clarify the biological mechanisms through which AEDs affect LGG prognosis. Our study established a reliable 13-gene AEDs-related LGG prognostic model. Carbamazepine, Oxcarbazepine and Lacosamide were supposed to improve the OS by inhibiting the hazard factor SCN9A. Phenobarbital was supposed to restrict the OS by inhibiting the identified protectors GRIN2C and GRIN3A. Molecular docking visualized the strong affinities between the above drugs and targets. Retrospective cohort further verified our speculation about the effect of the above drugs on the prognosis of LGG. In vitro experiments demonstrated that inhibiting SCN9A, a common targets for most AEDs, could suppress LGG cells malignant behaviors; while the suppression of GRIN2C and GRIN3A enhanced the malignant behaviors of LGG cells. This study provided guidance for individualized AEDs selection for LGG patients, and provide new insights into the potential biological functions and molecular mechanisms of AEDs affecting LGG.</p>","PeriodicalId":9023,"journal":{"name":"BMC Pharmacology & Toxicology","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2026-06-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13501820/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148257263","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Consumption of systemic antibiotics in a tertiary care hospital in Northern Sri Lanka: a five-year trend analysis.","authors":"Yalini Guruparan, Pavithra Meenadchisundaram, Saranya Amarasingam, Somasundaram Nithiyananda, Thiyahiny Sunil Navaratinaraja","doi":"10.1186/s40360-026-01169-1","DOIUrl":"10.1186/s40360-026-01169-1","url":null,"abstract":"<p><strong>Background: </strong>Surveillance of antimicrobial consumption helps to understand the pattern of antibiotic utilisation and plays an essential role in tackling antimicrobial resistance. However, a lack of an established surveillance system is a major challenge in combating antimicrobial resistance in low- and middle-income countries (LMICs). This study aimed to determine the pattern of systemic antibiotic consumption at the Teaching Hospital, Jaffna, using the World Health Organization (WHO) methodology for surveillance of antimicrobial consumption.</p><p><strong>Methods: </strong>A descriptive study of systemic antibiotic consumption was conducted at the Teaching Hospital, Jaffna, from 2018 to 2022. Supply data were analysed using the Anatomical Therapeutic Chemical (ATC)/defined daily dose (DDD) methodology. Antibiotic consumption volume was expressed in DDD, while outpatient and inpatient consumption rates were expressed as DDD/100 patients and DDD/100 admissions, respectively. The AWaRe (Access, Watch, and Reserve) classification and Drug Utilisation-90% (DU90%) were used to assess consumption patterns. Trends were assessed using curve estimation analysis. The Wilcoxon signed-rank test and Friedman test were performed to determine the significance of changes between years and over five years, respectively. A p value ≤ 0.05 was considered statistically significant.</p><p><strong>Results: </strong>Compared with 2018, overall antibiotic consumption showed a declining trend except in 2019. Oral antibiotics accounted for more than 80% of total consumption, and amoxicillin/clavulanic acid remained the most commonly consumed antibiotic. Access antibiotics accounted for over 70% of total consumption, with an Access-to-Watch ratio > 2 throughout the study period. The DU90% segment remained largely consistent, comprising 11-12 antibiotics. Curve estimation analysis showed non-linear trends in Access and Watch antibiotic consumption. Despite the decline in total antibiotic consumption, the inpatient antibiotic consumption significantly increased in 2021 compared with 2020 (p < 0.001).</p><p><strong>Conclusion: </strong>Analysis of antibiotic supply data showed that the overall pattern of antibiotic consumption remained consistent over a five-year period despite the changes that occurred during the COVID-19 pandemic. Establishing routine monitoring of antibiotic consumption using available data sources in hospitals provides basic information and insights into the problems. These findings could help to plan strategies to improve the antibiotic utilisation in LMICs.</p>","PeriodicalId":9023,"journal":{"name":"BMC Pharmacology & Toxicology","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2026-06-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13449454/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148257227","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}