Introduction Atrial fibrillation is the most common sustained cardiac arrhythmia, primarily caused by arrhythmogenic activity within the pulmonary veins (PVs). Enhanced ketone body utilization can prevent heart failure by reducing inflammation and oxidative stress, factors crucial for atrial fibrillation pathogenesis. However, the role of ketone bodies in PV arrhythmogenesis remains unclear. This study investigated the effect of 3-hydroxybutyrate (3-OHB), the most abundant ketone body, on PV arrhythmogenesis and explored the underlying mechanisms. Methods Using conventional microelectrodes and the patch-clamp technique, we analyzed electrophysiological characteristics and ionic currents in isolated rabbit PV tissues and single PV cardiomyocytes. Results The effects of 3-OHB (10 mM) on reactive oxygen species (ROS) production, calcium homeostasis, and phosphorylated calcium/calmodulin-dependent protein kinase II (CaMKII) expression were analyzed through confocal microscopy and Western blotting. The results indicated that 3-OHB dose-dependently reduced PV spontaneous activity, contractility and diastolic tension. However, these effects were blocked by KN93 and AIP, a CaMKII inhibitor. Moreover, 3-OHB reduced late sodium and L-type calcium currents in PV cardiomyocytes; these effects were blocked by KN93 and AIP. Furthermore, 3-OHB reduced cytosolic ROS levels and phosphorylated CaMKII expression. Conclusion 3-OHB prevents PV arrhythmogenesis by modulating ionic currents, reducing ROS production, and regulating CaMKII signaling. Thus, 3-OHB holds promise as an antiarrhythmic agent.

ALK mutations are key oncogenic drivers in non-small-cell lung cancer (NSCLC). Although ALK tyrosine kinase inhibitors (TKIs) elicit high initial response rates, relapse due to acquired resistance is common. Conventional approaches fail to resolve tumor heterogeneity and epigenetic control, necessitating multi-omic integration to dissect molecular differences between ALK-mutant and wild-type (WT) tumors. Single-cell RNA sequencing (scRNA-seq) and matched chromatin accessibility (scATAC-seq) data of 5 WT and 4 ALK-mutant NSCLC samples from GEO (GSE274934) were integrated. "Seurat" and "Harmony" packages in R were used for data preprocessing and batch correction. "Monocle" package reconstructed epithelial differentiation trajectories. "CellChat" package delineated cell-cell communication. "Signac" package integrated multiple omics data and analyzed the differentially accessible chromatin regions. Motif enrichment based on the JASPAR database identified key transcription factors. The role of CEACAM6 in the malignant progression of ALK-mutant-mutant NSCLC was assessed by qRT-PCR, CCK-8, colony formation, and wound-healing assays. ALK-mutant epithelial cells exhibit disrupted differentiation trajectories, characterized by loss of SPINK1 expression and pan-expression of MARCKSL1. ALK-mutant cells relied on CEACAM5/6 signaling for communication; WT cells primarily engaged in multi-directional MIF interactions. ALK-mutant cells showed increased global chromatin accessibility. Motif analysis revealed enrichment of PRC pathway components and EGR1 binding sites (survival/drug resistance-associated) in ALK-mutant cells, whereas WT cells specifically enriched KLF5, ZNF148, and GLIS3 motifs. In vitro, CEACAM6 expression was significantly upregulated in ALK-mutant compared to WT cells. CEACAM6 knockdown significantly inhibited cell proliferation and migration, and reduced p-AKT and EGR1 protein levels, indicating that CEACAM6 promotes malignant progression of ALK-mutant NSCLC through the AKT-EGR1 signaling axis. ALK mutations drive tumor stemness and drug resistance by blocking epithelial cell differentiation, activating CEACAM6-mediated signaling, enhancing chromatin accessibility, and remodeling the EGR1/PRC regulatory network. Targeting CEACAM6 and its downstream effector EGR1 may represent an effective strategy to overcome ALK-TKI resistance.

One serious consequence of sepsis that has a direct impact on patient outcomes is intestinal barrier disruption brought on by sepsis. Although the polyphenolic molecule resveratrol (RE) is well-known for its anti-inflammatory and antioxidant properties, it is unknown how it affects the NADPH oxidase 1 (NOX1)/sirtuin 1 (SIRT1) pathway and against intestinal barrier failure by sepsis. This work adopted a lipopolysaccharide (LPS)-treated Caco-2 cell and sepsis mice model (cecal ligation and puncture) to assess the protective effects of RE. We employed quantitative reverse transcription PCR, enzyme-linked immunosorbent assay, histological analysis, immunohistochemistry, and Western blot to assess survival rates, inflammatory cytokine levels, autophagy markers, and intestinal barrier function. The role of NOX1 and SIRT1 in RE-mediated protection was explored through NOX1 overexpression and related molecular analyses. RE significantly improved survival rates in sepsis mice, reduced inflammatory cytokines, and restored intestinal barrier function. RE reversed the increase of NOX1 and the decrease of SIRT1 observed in sepsis. Histological analysis showed that RE protected the intestinal structure, maintained the expression of tight junction proteins, and alleviated intestinal damage. In LPS-treated Caco-2 cells, RE inhibited inflammation, autophagy suppression, and reactive oxygen species (ROS) production. NOX1 overexpression partially reversed the protective effects of RE. By modifying the NOX1/SIRT1 signaling pathway, RE guards against intestinal barrier failure by sepsis. These results underline the critical involvement of the NOX1/SIRT1 pathway in autophagy and inflammation control and imply that RE may be a viable treatment approach for intestinal damage associated with sepsis.

Background: Wedelolactone (WED) is a polyphenolic compound with a coumarin skeleton isolated from marigold. Despite its wide application in traditional medicine, its mechanisms of action and safety profile require further investigation. Summary: The key contributions of this review lie in: (1) the first systematic integration of WED’s multi-target mechanisms across diseases through the AMPK/NF-κB/NLRP3 network; (2) clarification of its dose-effect relationship (effective therapeutic window: 5–100 mg/kg) and toxicity thresholds; (3) proposal of clinical translation strategies, including nanodelivery systems to address bioavailability issues. Recent studies revealed novel mechanisms such as WED’s inhibition of ferroptosis via GPX4 and modulation of the FXR-bile acid axis, demonstrating efficacy in acute lung injury and liver fibrosis. Key Messages: This article provides a comprehensive framework integrating mechanistic insights and translational research for WED’s clinical development.

Introduction: Escitalopram oxalate (ESC) was extensively reported to improve insomnia in patients with depression/anxiety. The serotonin transporter gene (SLC6A4) was involved in regulating insomnia. However, it is still unclear whether ESC improves insomnia by regulating SLC6A4 expression. Therefore, this study aimed to investigate whether ESC improves insomnia by regulating SLC6A4 based on clinical and animal experiments. Methods: The clinical and animal experiments were involved in this study. For clinical experiments, after all 110 participants were divided into four groups, the portable sleep electroencephalogram monitor, HAMA14 scale, and HAMD24 scale were used to evaluate patients’ sleep quality, anxiety, and depression. For animal experiments, after all 18 ICR male mice were randomly divided into three groups (n = 6), the sodium pentobarbital-induced sleeping test, locomotor activity test, elevated plus maze, and open field test were used to evaluate mice’s sleep quality and anxiety- and depression-like behaviors. The H&E staining was used to determine pathological injuries in mice’s hippocampal tissues. The ELISA kits were adopted to detect the 5-HT, norepinephrine (NE), gamma-aminobutyric acid (GABA), and glutamate (Glu) levels in the hypothalamus tissue and the corticotropin-releasing hormone (CRH), adrenocorticotropic hormone (ACTH), and cortisol (CORT) levels in the serum. The PubChem, DrugBank, and Therapeutic Target Database were employed to predict the potential targets of ESC. The immunohistochemical staining and Western blot were applied to assay the SLC6A4, 5-HTR1A, and 5-HTR2A expression levels in the hippocampal tissues of mice. Results: ESC shortened the sleep latency, extended the sleep time, enhanced the sleep efficiency, and improved anxiety and depression in patients and mice. ESC mitigated the pathological injuries in mice’s hippocampal tissues. ESC effectively regulated mice’s neurotransmitter levels and hypothalamic-pituitary-adrenal (HPA) axis homeostasis, including upregulating 5-HT and GABA and downregulating NE, Glu, CRH, ACTH, and CORT. Moreover, SLC6A4 was predicted as the potential target of ESC. ESC prominently inhibited SLC6A4 expression (p < 0.001) and regulated 5-HTR1A and 5-HTR2A expression (p < 0.001) in hippocampal tissues. Conclusion: Taken together, ESC was suitable for treating insomnia in the clinic and improved insomnia by targeting SLC6A4 to regulate the HPA axis in mice.

Background: Cancer remains a leading cause of mortality worldwide, necessitating innovative therapeutic strategies beyond conventional treatments. The increasing interest in natural and synthetic antiproliferative compounds is driven by their ability to target oncogenic pathways implicated in tumor progression, metastasis, and drug resistance. This review explores the potential of bioactive phytochemicals and molecularly targeted therapies, particularly epidermal growth factor receptor (EGFR) inhibitors, in modulating cancer cell survival, proliferation, and immune evasion. A central focus is placed on the phosphoinositide 3-kinases (PI3Ks)/protein kinase B (AKT), JAK/STAT, and mitogen-activated protein kinase (MEK)/extracellular signal-regulated kinase (ERK) signaling pathways, which are frequently dysregulated in therapy-resistant cancers, particularly head and neck cancer. Summary: Emerging evidence suggests that phytochemicals such as curcumin, resveratrol, and flavonoids not only suppress oncogenic signaling but also enhance apoptosis, inhibit epithelial-mesenchymal transition, and regulate oxidative stress responses. Additionally, recent preclinical and clinical studies indicate that combinatorial applications of phytochemicals with targeted agents can sensitize resistant tumors to chemotherapy and immunotherapy, thereby improving therapeutic efficacy. However, a major challenge limiting the clinical translation of phytochemicals is their low bioavailability and rapid metabolism. Advances in nanoparticle-based drug delivery, synthetic derivatives, and CRISPR-mediated genome editing offer promising solutions to overcome these limitations, ensuring optimal stability, targeted delivery, and enhanced anticancer activity. Key Messages: By integrating traditional phytotherapy with modern molecular oncology, this review highlights novel synergistic strategies that may revolutionize cancer treatment, paving the way for personalized anticancer therapeutics. DBCs and herbal medicine influence key oncogenic pathways, including EGFR, PI3K/AKT, and MEK/ERK. Human papillomavirus (HPV)-positive and HPV-negative tumors exhibit distinct molecular profiles, affecting their response to conventional treatments and adjunctive therapies. Polyphenols such as curcumin, resveratrol, and quercetin, along with herbal extracts including Scutellaria baicalensis and Camellia sinensis, demonstrate the ability to modulate oxidative stress, apoptosis, and immune responses while reducing therapy resistance. Nanoparticle-based formulations improve the bioavailability of these compounds, enhancing their anticancer effects. However, their effectiveness varies based on the HPV status of the tumor, with HPV-positive cancers showing greater sensitivity to immune-modulating compounds.

Introduction: Proton-pump inhibitor (PPI) monotherapy is standard for artificial ulcer healing after gastric endoscopic submucosal dissection, but evidence on the efficacy of PPI combined with gastric mucosal protectants remains inconclusive. This network meta-analysis aimed to compare the efficacy of 10 mucosal protectants combined with PPIs. Methods: We systematically searched PubMed, Embase, Cochrane Library, Web of Science, and ClinicalTrials.gov until January 2025. Included were 20 randomized controlled trials (n = 2,000) comparing PPI monotherapy versus PPI combined with protectants (e.g., rebamipide, ecabet, polaprezinc) or active controls. Primary outcomes included ulcer area reduction, healing rates (4/8 weeks), longest ulcer diameter, and bleeding risk. Frequentist random-effects models synthesized risk ratios (RRs) and MDs with 95% CIs. Consistency was evaluated using design-by-treatment interaction and node splitting. Risk of bias (RoB 2.0) was assessed at the outcome level. Certainty of evidence was graded with GRADE. Results: Bismuth subcitrate-magnesium granules (BMG) + PPI most effectively reduced 4-week ulcer area (MD: −62.50 mm2, 95% CI: −87.25 to −37.75 vs. PPI; SUCRA = 94%). Ecabet sodium (EB) + PPI achieved the highest 8-week healing rate (RR: 7.71, 95% CI: 5.52–9.91). Hydrotalcite (HT) + PPI best reduced ulcer diameter (MD: −1.87 mm), while teprenone (TN) + PPI optimally prevented bleeding (RR: −3.41, 95% CI: −5.43 to −1.38). Rebamipide + PPI showed efficacy heterogeneity, particularly in large ulcers (>40 mm). Conclusions: PPI-based combinations likely accelerate healing versus PPI alone, but conclusions are hypothesis generating given indirect evidence and regional concentration of trials. Combination therapy outperforms PPI monotherapy. BMG + PPI is optimal for early ulcer healing, EB + PPI for long-term healing, HT + PPI for diameter reduction, and TN + PPI for bleeding prevention. Stratified regimens by ulcer characteristics are recommended.

Introduction: The administration of medication through feeding tubes (FTs) represents a critical aspect of routine nursing practice. Although guidelines recommend the separate administration of medications to minimize potential interactions, it is common practice in the clinical settings for medications to be combined and administered simultaneously. Since there is a lack of data on this topic, this study assesses the stability of drugs crushed and mixed in water solution concurrently for administration through FT. Methods: The drug compatibility was evaluated in vitro by monitoring the changes in drug content in water solution over time and identifying potential degradation products using a high-performance liquid chromatography system. Results: The majority of drugs (acetylsalicylic acid, clopidogrel, atorvastatin, furosemide, and prasugrel) maintained their stability during the entire preparation process. The only medication that showed degradation over time was pantoprazole (especially when combined with acetylsalicylic acid and clopidogrel), which was attributed to the acidic environment. The remaining drugs (acetylsalicylic acid, clopidogrel, atorvastatin, furosemide, and prasugrel) maintained their stability during the entire preparation process. Conclusion: This study proves that most drugs can be prepared and administered simultaneously, with the exception of acid-labile drugs, which undergo significant degradation in acidic solutions.

Introduction: High-risk neuroblastoma is a difficult-to-treat cancer with high rates of recurrence and treatment resistance, likely driven by a population of cancer stem cells. Multiple previous studies have suggested that the use of mevalonate pathway inhibitors, such as statins and bisphosphonates, may have anticancer activity against high-risk tumors. Methods: We aimed to observe the use of mevalonate pathway inhibitors against the cancer stem cell population of high-risk neuroblastoma cell lines SH-SY5Y, SK-N-AS, and SK-N-BE(2)-C using spheroid-based assays. Results: We observed significant reductions in spheroid formation capability, stem cell frequency, and stemness properties of these neuroblastoma cancer stem cells with fluvastatin and zoledronate treatment. Conclusion: Treatment with mevalonate pathway inhibitors leads to reduced neuroblastoma cancer stem cell function through reductions in protein geranylgeranylation.

The article "Tanshinone IIA Affects Autophagy and Apoptosis of Glioma Cells by Inhibiting Phosphatidylinositol 3-Kinase/Akt/Mammalian Target of Rapamycin Signaling Pathway" [Pharmacology. 2017;99(3-4):188-195. https://doi.org/10.1159/000452340] by Lijuan Ding, Shudong Wang, Weiyao Wang, Peng Lv, Donghai Zhao, Feier Chen, Tianjiao Meng, Lihua Dong and Ling Qi has been retracted by the Publisher and the Editor.After the publication of this article, concerns were raised about the integrity of some of the data presented. Specifically, similar features appear between the two panels "FITC-A 740 Y-P" and "FITC-A Mixed" in Figure 3b of the article. In addition, panels in Figure 3b of this article are the same as panels in Figure 3 of another article by different authors, published subsequently in a different journal [1], specifically:Figure 3b panel "FITC-A Tan IIA" is the same as Figure 3c of [1].Figure 3b panel "FITC-A 740 Y-P" is the same as Figure 3a of [1].Figure 3b panel "FITC-A Mixed" is the same as Figure 3b of [1].The authors did not respond to requests to comment on the concerns and provide the raw data within the given timeframe despite multiple attempts of contact. We contacted the authors' institution to request an investigation. However, we did not receive a response. Given the severity of the concerns raised, this article is being retracted. The authors have not responded to our correspondence regarding this retraction despite multiple attempts of contact.