Although the use of bispecific antibodies for relapsed/refractory diffuse large B-cell lymphoma (R/R DLBCL) is expanding, reports of pseudoprogression following this therapy are scarce. A 58-year-old, male patient with DLBCL achieved a complete response (CR) after fourth-line therapy with lisocabtagene maraleucel. However, 26 months post-infusion, he experienced the development of pelvic lymphadenopathy, which was histologically confirmed as a relapse. Because the disease was refractory to radiotherapy and chemotherapy, epcoritamab was administered as the seventh-line treatment. A fever developing after the second step-up dose (Cycle 1, day 12) was diagnosed as grade 1 cytokine release syndrome and was treated with acetaminophen. Nonetheless, the fever was still present on day 14, when abdominal pain requiring opioid administration also developed. Computed tomography (CT) revealed enlargement of the pelvic lesions and increased ascites. Cytology of the ascites revealed no lymphoma cells and showed a predominantly inflammatory cell composition, while lactate dehydrogenase levels decreased, supporting the diagnosis of pseudoprogression. The treatment was continued and his symptoms gradually improved. After three cycles, positron emission tomography-CT confirmed the complete metabolic response (CMR), which was maintained through nine cycles. The present case highlights the potential for pseudoprogression to occur during epcoritamab therapy, suggesting that continued treatment may lead to durable remission even in patients with early clinical deterioration.

Glycosylation commonly inactivates macrolide antibiotics, and the resulting glycosides are largely dismissed as inactive waste products. Whether such molecules retain hidden therapeutic potential remains underexplored. Here, we address this question using spiramycin I 2'-O-glucopyranoside as a proof-of-concept model. The glycoside was enzymatically synthesized via OleD and structurally confirmed by NMR and HR-ESI-MS. Activity evaluation showed that glycosylation at the 2'-OH position abolished antibacterial activity, adding a new example to glycosylation-mediated antibiotic inactivation. To explore whether this inactivated glycoside harbors alternative functions, we performed in silico target fishing and reverse docking. These approaches identified glutathione S-transferase P (GSTP1) as a high-confidence target, a prediction further supported by molecular dynamics simulations and MM/PBSA calculations. Guided by this hypothesis, we evaluated the glycoside in an acetaminophen (APAP)-induced HepG2 hepatocyte injury model and found that it significantly attenuated cell death, whereas the parent antibiotic exacerbated cytotoxicity. Moreover, glycosylation led to a markedly higher solubility. These findings demonstrate that antibacterially inert glycosides can retain valuable non-antibiotic activities, exemplified here by hepatoprotection via GSTP1 engagement. Beyond this specific case, our study establishes a paradigm for repurposing inactivated antibiotic glycosides as a previously overlooked source of bioactive molecules, advocating for broader re-evaluation of such "waste" metabolites in drug discovery.

Cardiovascular disease (CVD) and chronic pain are leading causes of morbidity and functional disability worldwide, and there is increasing evidence demonstrating that chronic pain may elevate the risk for major adverse cardiac and cerebrovascular events. Given the intertwined nature of the cardiovascular and pain regulatory systems, medications used for chronic pain management may also contribute to the risk of cardiac events due to their cardiovascular side effects. This literature review critically evaluates the impact of the most commonly prescribed pain medications on the cardiovascular system. Medications discussed include non-steroidal anti-inflammatory drugs (NSAIDS), acetaminophen, opioids, antidepressants, gabapentinoids, and intra-articular injections. In each case, factors such as dosage and patient predispositions are considered in how they change a clinician's response in order to achieve the best patient outcome. A comprehensive literature search was performed on multiple databases, including PubMed, Google Scholar, and ScienceDirect, up to April 2026. For each drug class, cardiovascular risk was evaluated in the context of dosage and patient-specific predisposing factors, and weighed against the degree of pain relief provided. By drawing attention to this issue, our aim is to enhance understanding of drug mechanisms and identify appropriate treatment options, ultimately fostering better clinical practices and evidence-based initiatives in this healthcare endeavor.

Acetaminophen (APAP) also known as paracetamol, is the only antipyretic and analgesic agent that can be administered to pregnant women. In addition to hepatotoxicity in cases of an overdose, the developmental neurotoxicity of APAP has been reported in model organisms. In this study, developing zebrafish were used to assess the neurotoxic effects of waterborne APAP exposure (0.039-2.5 mM). At 120 hpf, the spontaneous swimming distance was significantly reduced at all tested APAP concentrations under alternating light-dark conditions. Touch-evoked escape velocity, which assesses the motor function, was not significantly affected at any concentration and it increased at moderate APAP doses. The optokinetic response was only reduced at 2.5 mM APAP concentrations, suggesting that the decrease in spontaneous swimming at low APAP doses is unlikely to be due to motor or visual impairments. Vibration-evoked responses, indicative of the sensory function, were slightly but significantly diminished at 0.625 and 2.5 mM APAP concentrations. At 72 h post-fertilization (hpf), acridine orange and terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) staining showed that exposure to 2.5 mM APAP resulted in regulated cell death in the cerebellum, retina, and dorsal trunk. Some APAP-induced cell death in the dorsal trunk was confirmed to be of neuronal origin using Tg(eno2:Cerulean) transgenic zebrafish. N-acetylcysteine, a well-known antioxidant and antidote for APAP toxicosis in humans, partially attenuated APAP-induced cell death. These results suggest that APAP induces developmental neurobehavioral and sensory organ toxicity in the absence of detectable regulated cell death under the present experimental conditions.

The relentless release of pharmaceutical antibiotics into water bodies demands robust and reusable photocatalysts. Herein, a hierarchical ZIF-67@Co-HOF-x heterostructure is synthesized through the in-situ growth of ZIF-67 onto a pre-formed cobalt-based hydrogen-bonded organic framework (Co-HOF). Among the series, ZIF-67@Co-HOF-200 exhibits uniform dispersion, intimate interfacial contact, and enhanced charge separation, as demonstrated by XRD, FTIR, SEM-EDS, TEM, XPS, PL, EIS, and TGA analyses. DFT calculations further reveal strong interfacial electronic coupling, with CDD, ELF, and Bader analyses confirming charge redistribution across the ZIF-67/Co-HOF interface. Compared with pristine components, the heterostructure exhibits enhanced visible-light absorption with a narrowed band gap of 2.01 eV, suppressed photoluminescence, and reduced charge-transfer resistance. Under optimized conditions (pH 7, catalyst dosage 0.5 g L[-1], and initial TCH concentration of 20 ppm), ZIF-67@Co-HOF-200 achieves 98% TCH degradation within 60 min following pseudo-first-order kinetics (k = 0.06,144 min[-1]). The catalyst also demonstrates excellent versatility toward paracetamol, methyl orange, and Congo red, while maintaining 79% TCH removal efficiency under simulated wastewater conditions. Molecular interaction calculations further reveal favorable TCH and O2 accessibility at the heterointerface, supporting efficient pollutant degradation and ROS generation. The catalyst retains 94% of its initial activity after four consecutive cycles, demonstrating excellent stability. Mechanistic investigations identify O2•[-] and h[+] as dominant reactive species during degradation. This work provides a rational strategy for constructing MOF/HOF heterostructures with enhanced interfacial charge regulation for visible-light-driven wastewater remediation.

Dental opioid prescriptions remain one of the most common initial exposures to opioids worldwide. Although opioid prescribing in dentistry has declined, even limited exposure to opioids may be a significant risk factor for developing Opioid Use Disorder (OUD), particularly in younger populations. This review evaluates the existing literature on dental opioid prescriptions and the development of OUD, identifies procedural and patient-related risk factors, and assesses the effectiveness of existing intervention strategies. Following the PRISMA guidelines, a comprehensive literature search was conducted across MEDLINE, Embase, PsycINFO, Web of Science, and CENTRAL from January 2011 to July 2026. Eligible studies examined opioid prescribing in dental alveolar surgeries, related OUD/SUD outcomes, and preventative interventions. From an initial 1008 identified records, 12 studies met the final inclusion criteria for qualitative synthesis. Observational studies showed that factors significantly associated with persistent opioid use or adverse outcomes included higher prescribed opioid doses, prior substance use disorder, public or Medicaid insurance, younger age, female sex, and complex chronic medical conditions. Notably, patients undergoing low-pain dental procedures who received opioids demonstrated the highest relative risk for short-term persistent use. Five studies evaluated interventions, finding that short behavioral counseling and opioid-sparing pharmacologic strategies, specifically liposomal bupivacaine and preemptive intravenous paracetamol, effectively reduced postoperative opioid consumption. However, none of the included intervention studies had sufficient follow-up to evaluate the direct prevention of clinical OUD. Future research should prioritize prospective longitudinal studies and randomized controlled trials to evaluate interventions that safely reduce opioid exposure and definitively prevent OUD following dental procedures.

An electrochemical sensor based on a novel composite of electrochemically reduced graphene oxide, polypyrrole-coated magnetic nanoparticles (MNPs@PPy), and Nafion was developed for dopamine (DA) detection. The structural, thermal, and electrochemical properties of the composite were validated through a combination of advanced spectroscopic techniques, thermal profiling, electron microscopy, and impedance analyses. Under optimized conditions, differential pulse voltammetry (DPV) revealed a high sensitivity (1.573 A·M[-1]·cm[-2], R[2] = 0.9874) and a limit of detection (LOD) of 5.4 × 10[-9] M for DA. The sensor displayed excellent selectivity, showing minimal interference from ascorbic acid, uric acid, and acetaminophen. Repeatability and reproducibility were confirmed (coefficient of variation ~8%). Real-sample analysis of urine and blood demonstrated recovery rates between 75 and 116%.

Natural Killer (NK) cell-mediated immunosurveillance is a cornerstone of anti-tumor defense, yet its efficacy can be compromised by common clinical medications. Paracetamol (APAP) and metformin (MET) are widely used for pain and metabolic management in cancer patients, but their unintended effects on the immune-tumor interface remain poorly understood. MCF-7 breast cancer cells (Luminal A subtype) were treated with APAP or MET and co-cultured with primary expanded NK cells (CD3[-]CD56[+]CD16[+]). We evaluated cell proliferation, cell cycle distribution, and the enrichment of the CD44[+]CD24[-] cancer stem-like cell (CSC-like) subpopulation. Transcriptional changes in immune checkpoints (PD-L1/L2), stress ligands (MICA/B), and costimulatory molecules CD80/86 were quantified via RT-qPCR. Despite inhibiting MCF-7 growth (IC50 at 48 h: 11.86 mM for APAP; 21.11 mM for MET), both drugs induced a "therapeutic paradox" by promoting an immune-evasive phenotype. APAP and MET significantly enriched the CD44[+]CD24[-] CSC-like subpopulation to 75.31% and 68.31%, respectively, compared to 11.00% in controls. Molecular analysis revealed a robust upregulation of PD-L1 (19.9-fold by APAP) and PD-L2 (16.4-fold by MET), alongside increased CD80/86 and MICA/B transcription. Consequently, drug-treated cells exhibited marked resistance to NK-mediated apoptosis and necrosis. NK cells preferentially eliminated non-stem cells (non-CSCs), inadvertently further concentrating the highly resistant CSC-like subpopulation. Additional experiments revealed that APAP directly impaired NK-cell survival and reduced the proportion of CD3[-]CD56[+] cells, whereas MET exerted minimal effects on NK cells, suggesting distinct mechanisms underlying the observed reduction in NK-mediated cytotoxicity. Under the experimental conditions employed in this study, APAP and MET were associated with reduced susceptibility of MCF-7 cells to NK-mediated killing through distinct but partially overlapping mechanisms, including CSC-like enrichment and transcriptional activation of immune-evasion pathways. Although these findings were obtained in a mechanistic in vitro model using supra-physiological drug concentrations, they identify potential mechanisms that warrant further validation in physiologically relevant experimental systems and in vivo models.

Objective: Our objective was to compare clinical safety and postoperative efficacy between transvesicoscopic Politano-Leadbetter (TPL) and laparoscopic Lich-Gregoir (LLG) ureteral reimplantation in infants and toddlers under 36 months diagnosed with primary obstructive megaureter (POM). Methods: This was a single-center retrospective cohort study of pediatric patients with POM who underwent ureteral reimplantation between January 2018 and April 2025. Patients were stratified into TPL and LLG groups by surgical approach. Baseline characteristics, perioperative outcomes, perioperative complications, imaging findings, renal functional outcomes, and long-term complications were collected and analyzed. Primary group comparisons were unadjusted, with additional multivariable linear regression performed for operative duration. Results: We enrolled 65 children: 30 in the TPL group and 35 in the LLG group. Baseline characteristics showed no statistically significant differences across the two study cohorts. There were no open conversions in either group. Total operative duration did not differ significantly between the TPL and LLG groups (145.8 ± 30.6 min vs. 136.9 ± 25.2 min; mean difference, 8.9 min; 95% CI, -4.9 to 22.7; p = 0.210). In multivariable linear regression, TPL showed a non-significant trend toward longer operative time after adjustment for age, preoperative ureteral diameter, and surgery year (B = 10.4 min; 95% CI, -3.7 to 24.4; p = 0.141). Time to postoperative oral intake was slightly shorter in the TPL group (6.1 ± 2.3 h vs. 8.2 ± 2.9 h; mean difference, -2.1 h; 95% CI, -3.4 to -0.8; p = 0.002). No statistically significant differences were detected in estimated blood loss, ureteral tapering rate, double-J stent placement rate, postoperative pain score, acetaminophen use, urinary catheterization duration, or length of hospital stay. Perioperative complications occurred in 3 patients in the TPL group and 5 patients in the LLG group (10.0% vs. 14.3%; risk difference, -4.3%; 95% CI, -20.1% to 11.5%; p = 0.716). No Clavien-Dindo grade III or higher complications occurred in either group. During follow-up, both groups showed reductions in anteroposterior pelvic diameter (APD) and ureteral diameter (UD), with preserved differential renal function (DRF). Low-grade postoperative vesicoureteral reflux (VUR) was detected in two LLG patients, including one grade I case at 4 months and one grade II case at 6 months after surgery; both were managed conservatively. Neither group experienced recurrent ureterovesical junction obstruction (UVJO) nor required reoperation during follow-up. Conclusions: In this single-center retrospective cohort of infants and toddlers with POM, no statistically significant differences were detected in the main perioperative and follow-up outcomes between TPL and LLG. TPL enables intravesical reconstruction and better preserves the natural anatomical course of the ureter and may serve as an alternative minimally invasive option for this patient population.