Search Results (873)

Vitamin C (L-ascorbic acid) is an essential micronutrient involved in collagen biosynthesis, redox regulation, immune function, endothelial biology, carnitine synthesis, neurotransmitter metabolism, and non-heme iron absorption. Dietary reference values are designed primarily to prevent deficiency in general populations, but vulnerability to low-vitamin C status may increase during trauma, surgery, chronic inflammation, malignancy, metabolic disease, smoking, poor intake, environmental exposure, and tissue repair. This narrative review synthesizes mechanistic, pharmacokinetic, clinical, and safety evidence on vitamin C as a stress-responsive micronutrient. Evidence is reviewed across tissue repair and wound healing, orthopedic recovery and selected complex regional pain syndrome risk contexts, fatigue, neuropsychiatric vulnerability, cancer-supportive care, vascular homeostasis, dermatologic biology, and preliminary microbiota–gut–brain axis hypotheses. The strength of evidence differs substantially across domains: biochemical functions and deficiency correction are well established, whereas benefits of supraphysiologic oral supplementation in vitamin C-replete patients remain uncertain. Oral nutritional supplementation is distinguished from intravenous pharmacologic ascorbate, with attention to route, formulation, dose division, gastrointestinal tolerance-limited adjustment, and safety monitoring. Because evidence for high-dose oral supplementation remains limited and condition-specific, such use should be individualized, time-limited, and clinician-monitored rather than presented as a population-level recommendation or evidence-defined therapeutic target. Taken together, the clinical value of vitamin C depends on baseline status, patient vulnerability, route, formulation, dosing interval, clinical endpoint, and safety review. Full article

Background/Objectives: Selecting appropriate doses for pediatric patients remains one of the most complex challenges in drug development because developmental changes in physiology, metabolism, organ function, and pharmacodynamics substantially influence drug exposure and response. This review summarizes current evidence-based approaches to pediatric dose selection across the developmental continuum and evaluates contemporary model-informed strategies for individualized dosing. Methods: A narrative review of the literature was conducted focusing on pediatric dose-scaling methodologies, developmental pharmacology, physiologically based pharmacokinetic (PBPK) modeling, population pharmacokinetic (PopPK) approaches, exposure–response analysis, therapeutic drug monitoring, and regulatory extrapolation frameworks. Special populations and clinical scenarios relevant to pediatric dose optimization were also evaluated. Results: Simple body weight-based scaling from adult doses inadequately accounts for developmental changes in drug disposition and response. Allometric scaling combined with maturation functions provides improved dose prediction in neonates and infants, while PBPK and PopPK modeling support mechanistic and data-driven dose optimization across pediatric age groups. Fat-free-mass (FFM)-based scaling is preferred over total body weight for many drugs in children with obesity. Additional considerations including obesity, biologics, formulation and excipient safety, pharmacogenomics, critical illness, therapeutic hypothermia, extracorporeal support, therapeutic drug monitoring, and drug–drug interactions substantially influence pediatric dosing strategies. Regulatory frameworks including ICH E11A increasingly support model-informed pediatric extrapolation and precision dosing approaches. Conclusions: Pediatric dose selection has evolved from empirical weight-based dosing toward integrated model-informed strategies incorporating developmental physiology, pharmacometrics, and regulatory science. Allometry, maturation functions, FFM-based scaling, PBPK, PopPK, and therapeutic drug monitoring provide complementary tools for rational pediatric dose optimization, although drug- and pathway-specific validation remains essential, particularly in neonates and critically ill children. Full article

Objectives: AC02, a novel synthetic peptide derived from ACTH, is being developed as a potential therapeutic alternative to porcine ACTH_1-39 for use in infantile spasms. Methods: The study comprised single-ascending dose cohorts (0.02, 0.04, 0.08, 0.16 mg/kg AC02) and multiple-ascending dose cohorts (0.04, 0.08 mg/kg AC02 daily for 5 days). A separate positive-control arm received porcine ACTH_1-39 (25 U/day for 5 days). PD effects (free and total cortisol) were compared head-to-head with the positive control. Plasma concentrations of AC02, porcine ACTH_1-39, free and total cortisol were quantified by validated LC-MS/MS methods, and anti-drug antibody responses were measured using a validated electrochemiluminescence bridging immunoassay. Population PK/PD modeling characterized the concentration–response relationships for free cortisol. Results: Across the 0.02–0.16 mg/kg dose range, AC02 exhibited approximately dose-proportional pharmacokinetics and no accumulation after multiple doses. At 0.04 and 0.08 mg/kg, the baseline-corrected effects on free cortisol were generally consistent with those of porcine ACTH_1-39. Dynamic monitoring of the free cortisol fraction revealed a biphasic pattern across all groups: an early peak followed by a later rise. Total cortisol, by contrast, showed only a monophasic decline, indicating the limitations of total cortisol as a sole PD biomarker. No unexpected safety signals were observed. At 0.04 mg/kg, AC02 demonstrated pharmacodynamic responses comparable to those of marketed ACTH product based on the biologically active component of free cortisol, with favorable safety and pharmacokinetic profiles. Conclusions: This first-in-human study demonstrates that AC02 has favorable pharmacokinetic properties, and an acceptable safety profile. Full article

Background: Gender medicine is an emerging approach that recognizes how biological sex, gender identity, and sociocultural roles influence health and disease. These factors can significantly affect prevention, screening, diagnosis, and treatment outcomes. In oncology, accumulating evidence highlights sex-based differences in cancer incidence, therapeutic response, and treatment-related adverse events. A comprehensive gender-based approach should also address the specific needs of sexual and gender minority (SGM) populations. Based on the existing literature and the authors’ expertise, this perspective paper provides an overview of this topic, emphasizing its importance, discussing current challenges, and proposing potential future directions for research and clinical practice. The literature discussed in this article was selected through a narrative, rather than a systematic, approach and is intended to provide the scientific context supporting the authors’ perspective and interpretation of the current evidence. Methods: To investigate gender differences in oncology regarding epidemiological data, we queried the AIRTUM and GLOBOCAN databases. Furthermore, we conducted a bibliography search of scientific papers by querying PubMed/MEDLINE to explore gender differences, in particular regarding treatments. The database was searched by looking for papers published between 1 January 2022 and 31 December 2025. Results: Cancers affecting both sexes show higher incidence and mortality rates in men, a trend observed worldwide and confirmed by national data. However, important sex-related differences also emerge in treatment response. Women appear to derive a smaller survival benefit than men from immunotherapy alone but may experience greater benefit when immunotherapy is combined with chemotherapy. These differences may be explained by distinct molecular mechanisms underlying antitumor immune responses in males and females. Furthermore, women experience higher rates of treatment-related toxicities, likely due to sex-specific differences in pharmacokinetics and pharmacodynamics. Conclusions: Integrating sex and gender perspectives into oncology is essential for advancing personalized medicine and improving patient care. Understanding biological differences can help optimize treatment selection and dosing strategies, thereby enhancing efficacy while minimizing adverse effects. At the same time, addressing gender-related factors may improve psychosocial support, patient well-being, and treatment adherence. Achieving these goals requires coordinated efforts, including sex-disaggregated research, gender-sensitive clinical protocols, and healthcare policies aimed at reducing gender disparities in cancer care. Full article

Background/Objectives: Faricimab is a novel bispecific antibody simultaneously inhibiting vascular endothelial growth factor-A (VEGF-A) and angiopoietin-2 (Ang-2). Its efficacy in vitrectomized eyes with diabetic macular edema (DME), a setting with altered intravitreal pharmacokinetics, remains poorly characterized. We evaluated the 12-month outcomes of intravitreal faricimab (IVF) for DME in eyes vitrectomized for proliferative diabetic retinopathy (PDR). Methods: We retrospectively reviewed 12 consecutive eyes of 11 patients (mean age 59.4 ± 10.5 years) with DME after pars plana vitrectomy (PPV) for PDR who received IVF (6 mg/0.05 mL) between September 2022 and August 2024 with at least 12 months of follow-up. Best-corrected visual acuity (BCVA, logMAR) and central retinal thickness (CRT) were assessed at baseline (BL), 6 months (M6), and 12 months (M12). Results: Eight eyes were treatment-naïve and 4 had been switched from prior anti-VEGF therapy. Two eyes (16.7%) required a change in therapy: one for intraocular inflammation and one for inadequate anatomical response. In the 10 eyes that continued IVF, the mean number of injections was 4.1 ± 1.9. CRT decreased significantly from 489.5 ± 95.9 µm at BL to 328.5 ± 74.7 µm at M6 (p = 0.0065) and 307.0 ± 64.3 µm at M12 (p = 0.0023; repeated-measures ANOVA with Dunnett’s post hoc test). Mean BCVA improved from 0.33 ± 0.26 to 0.23 ± 0.21 logMAR at M12 (p = 0.0894). Conclusions: In this small retrospective study of vitrectomized eyes with DME after PPV for PDR, IVF was associated with significant anatomical improvement, while visual acuity remained stable over 12 months, with a relatively low injection burden. Faricimab may be a useful therapeutic option in this challenging population, although larger prospective studies are warranted to confirm these findings. Full article

Intranasal corticosteroids (INCS) remain the cornerstone of pharmacologic treatment for allergic rhinitis (AR) because of their well-established anti-inflammatory efficacy and generally favorable benefit–risk profile. Nevertheless, concerns regarding local and systemic corticosteroid-related adverse events (AEs) continue to influence patient adherence, prescribing practices, and long-term treatment acceptance. In routine clinical practice, safety perception and corticosteroid-related concerns frequently influence adherence and formulation selection to a greater extent than differences in clinical efficacy, particularly in pediatric populations and in patients requiring prolonged continuous therapy. Differences in pharmacokinetic and pharmacodynamic properties, including systemic bioavailability, glucocorticoid receptor affinity, lipophilicity, protein binding, and extent of first-pass metabolism, are considered important safety profile determinants of currently available INCS formulations. Available evidence indicates that local AEs, particularly epistaxis, nasal irritation, dryness, and sensory discomfort, represent the most frequently reported treatment-related AEs across INCS formulations, although these events are generally mild, self-limiting, and infrequently treatment-limiting. Clinically significant structural nasal complications, including septal perforation or progressive mucosal injury, appear uncommon in currently available studies. Systemic AEs, including hypothalamic–pituitary–adrenal (HPA) axis suppression, ocular toxicity, growth impairment, or clinically meaningful effects on bone metabolism, have not been consistently demonstrated with currently used low-systemic-exposure formulations administered at recommended therapeutic doses. Although systemic glucocorticoid exposure has been associated with alterations in lipid metabolism, adipose tissue function, and metabolic homeostasis, currently available intranasal corticosteroids demonstrate minimal systemic exposure, making clinically relevant metabolic effects unlikely under recommended therapeutic conditions. Formulations such as mometasone furoate, fluticasone propionate, fluticasone furoate, and ciclesonide exhibit pharmacokinetic characteristics associated with minimal systemic exposure because of extensive first-pass metabolism and low oral bioavailability. Although substantial pharmacokinetic differences exist between currently available INCS formulations, direct comparative evidence demonstrating clinically meaningful superiority in systemic safety outcomes remains limited. Current evidence suggests that formulation-dependent differences are clinically more relevant with respect to local tolerability, sensory characteristics, patient preference, and long-term adherence than major systemic safety outcomes. Pediatric evidence is generally reassuring, although historical concerns regarding growth suppression associated with earlier corticosteroid formulations continue to influence clinical practice. Currently available evidence supports the use of modern INCS as effective and generally well-tolerated therapeutic options across adult and pediatric populations. Full article

Background/Objectives: Polyethylene glycol (PEG) is widely used to enhance the stability and pharmacokinetics of nanomedicines, including lipid nanoparticle (LNP)-based mRNA vaccines. However, both pre-existing and vaccine-induced anti-PEG antibodies may compromise the efficacy and safety of PEGylated therapeutics. Methods: In this study, we analyzed the specificity and avidity of anti-PEG antibodies in human blood donor samples from Unvaccinated individuals and recipients of PEGylated mRNA-LNP vaccines (Comirnaty and Spikevax), polysorbate-containing vaccines, or vaccines lacking both PEG and polysorbates. Quantitative ELISA was used to characterize anti-PEG and anti-polysorbate IgM and IgG responses in 325 plasma samples, while an equilibrium titration method was applied to assess IgG binding to PEG molecules, micelles, and PEGylated liposomes with defined structural features in 36 plasma samples. Results: Vaccination with PEGylated mRNA-LNPs was associated with increased anti-PEG antibody levels and qualitative changes in antibody binding behavior. Anti-PEG IgG antibodies displayed progressively higher avidity toward larger and structurally more complex PEG-containing antigens, with the strongest binding observed for PEGylated liposomes. Notably, vaccinated individuals, particularly those who received Spikevax, showed increased end-group and backbone-specific avidity, as well as an enhanced ability of antibody paratopes to engage shorter PEG chains. In contrast, polysorbate-containing or PEG-free vaccines did not elicit comparable effects. Conclusions: These findings suggest that vaccination with PEGylated mRNA-LNPs is associated with the emergence of altered antibody populations with increased end-group reactivity and higher avidity toward PEG-directed immune responses, despite PEG being a synthetic, nonprotein polymer. Antibody binding to LNPs, accompanied by the emergence of high-avidity anti-PEG IgG seems to be consistent with an increased risk of adverse events, particularly following repeated vaccinations, including complement activation-related pseudoallergy (CARPA) and anaphylaxis. It may also contribute to altered immune protection against the vaccine target, underscoring the need for avidity-aware risk-benefit assessment of PEGylated therapeutics. Full article

Background: Hyperuricemia is an adverse effect frequently observed during favipiravir treatment. The time course, from uric acid elevation to recovery, and quantitative relationship between drug exposure and changes in serum uric acid levels remain insufficiently characterized. We investigated the pharmacodynamic mechanism of uric acid elevation and described its time course by population pharmacokinetic and pharmacodynamic modelling. Methods: Patients who received favipiravir for coronavirus disease 2019 or severe fever with thrombocytopenia syndrome were retrospectively evaluated. The pharmacokinetics of favipiravir were described by a one-compartment model with first-order absorption and elimination. Metabolite concentrations were predicted based on previously reported values. Changes in serum uric acid levels were described by a turnover model with zero-order production and first-order elimination. The drug effect was implemented as inhibition of the uric acid elimination process. Simulations based on the final model were performed for 10 consecutive days after the clinical regimen, with a 21-day follow-up. Results: The final model supported the inhibition of uric acid elimination by favipiravir and its metabolite. Regarding simulations, serum uric acid levels reached a median peak of 6.93 mg/dL at 6.7 days after treatment initiation and returned to pre-treatment levels within 4.0 days after treatment discontinuation. Conclusions: This combined population pharmacokinetic and pharmacodynamic turnover model quantified favipiravir-associated increases in serum uric acid levels and showed a transient profile with rapid recovery after drug discontinuation. These findings underscore the need for monitoring serum uric acid levels during favipiravir treatment, particularly in patients at a higher risk of gout. Full article

Background/Objectives: Special populations, including pediatric, geriatric, and organ-impaired patients, are consistently underrepresented in randomized controlled trials (RCTs), resulting in limited evidence for safe and effective dosing. Off-label use is common, and variability in drug exposure and response increases the risk of adverse drug reactions (ADRs). This review aims to examine how integrating pharmacometrics (PMX) with real-world data (RWD) can address evidence gaps by supporting dose optimization, population expansion, and safety evaluation in these vulnerable groups. Methods: A narrative literature review was conducted using PubMed, Embase, and Web of Science (January 2000–November 2025). Using Boolean combinations of PMX and RWD-related search terms, approximately 200–300 records were identified across the three databases; approximately 30 full-text articles were reviewed, and representative case studies were selected based on population diversity, methodological variation, and regulatory or clinical impact. Results: RWD–PMX integration has been applied across three domains: (i) dosing optimization through therapeutic drug monitoring (TDM)-informed PopPK modeling and model external validation in pediatric and neonatal populations; (ii) population expansion supporting dose extrapolation and regulatory decision-making for unapproved groups; and (iii) safety evaluation enabling identification of exposure–toxicity risk factors in vulnerable cohorts. Conclusions: Integrating PMX with RWD provides a practical and mechanistically grounded framework for evaluating dosing, treatment eligibility, and safety in populations insufficiently represented in clinical trials. Accumulating evidence indicates that RWD–PMX methodologies can complement traditional clinical research and inform regulatory decision-making. Continued refinement of data quality standards, validation practices, and guidance frameworks will be essential for broader adoption. Full article

Background: Adverse drug reactions (ADRs) represent a major and often underestimated source of morbidity, hospitalization, and functional decline in older adults. The convergence of age-related pharmacokinetic and pharmacodynamic changes, multimorbidity, polypharmacy, and frailty creates a clinical environment in which ADR risk is not static but evolves along progressive trajectories—from mild, early manifestations toward severe, potentially irreversible outcomes. Understanding these trajectories is essential for rational geriatric prescribing. Methods: This narrative review synthesizes evidence from epidemiological studies, systematic reviews, Cochrane analyses, and clinical trials published between 2000 and 2025, focusing on adults aged 65 years and older with two or more chronic conditions. Sources were identified through a structured, non-systematic literature search of PubMed, EMBASE, Cochrane Library, Web of Science, and Scopus using the terms ‘adverse drug reactions’, ‘polypharmacy’, ‘multimorbidity’, ‘frailty’, ‘deprescribing’, and ‘pharmacokinetics’ in older adults, alone and in combination. Evidence quality was assessed narratively, distinguishing trial evidence from observational and expert consensus data. Results: ADRs in older adults are best classified using complementary frameworks—the augmented Type A to withdrawal Type E and failure-of-therapy Type F taxonomy (Types A–F), the Dose-Time-Susceptibility (DoTS) classification, and the EIDOS mechanistic scheme—which together capture the heterogeneity of drug-related harm in this population. Age-related pharmacokinetic changes (altered absorption, increased volume of distribution of lipophilic drugs, reduced hepatic and renal clearance) and pharmacodynamic shifts (heightened receptor sensitivity, baroreflex impairment, increased blood–brain barrier permeability) interact with polypharmacy and frailty to amplify ADR trajectories from mild to severe. Anticholinergic burden, prescribing cascades, and inappropriate polypharmacy function as structural accelerators of these trajectories. Medication review and deprescribing improve prescribing quality but evidence for hard outcome benefits remains of low to very low certainty. Emerging AI-enabled digital tools show promising accuracy for identifying frailty and pharmacological vulnerability, but this performance relates to frailty classification and has not yet been shown to prevent ADR trajectories; they require validation for routine clinical use. Conclusions: Recognizing ADRs in older adults as dynamic trajectories rather than isolated events repositions prescribing review and deprescribing from optional to essential clinical acts. An integrated approach combining pharmacological vigilance, comprehensive geriatric assessment, structured deprescribing, and emerging digital decision-support tools offers the most realistic pathway to reduce the trajectory-related burden of drug-related harm in complex older patients. Full article

Background: Prostate cancer remains one of the most prevalent malignancies worldwide, with high mortality in advanced and metastatic stages. Drug repurposing offers a cost-effective and time-efficient strategy to identify new therapeutic options. Objectives: This study aimed to apply physiologically based pharmacokinetic (PBPK) modeling to evaluate repurposed antiretroviral drugs efavirenz (EFV), etravirine (ETV), and saquinavir (SAQ) in prostate cancer, and to assess potential drug–drug interactions (DDIs) between EFV and ETV. Methods: PBPK models for EFV and SAQ were obtained and an ETV was developed and validated using literature and ADMET Predictor^® data. Prostate tissue models were modified to simulate malignant conditions, and population-based simulations examined the influence of age and obesity. The GastroPlus^® DDI module was applied to explore mechanistic interactions between EFV and ETV under different physiological scenarios. Results: Tumor-specific prostate tissue alterations produced minimal systemic pharmacokinetic changes but increased total drug accumulated in simulated tissue, with differences in unbound concentrations, while demographic variables such as age and weight significantly affected drug exposure, which are comorbidities in prostate cancer. Lighter individuals exhibited higher plasma concentrations across all drugs, consistent with known previously reported pharmacokinetic trends in obese individuals. DDI simulations indicated only minor changes in ETV pharmacokinetics when combined with EFV, with no clinically significant interaction detected. Conclusions: The integration of PBPK modeling, population variability, and DDI analysis highlights the potential of SAQ, EFV, and ETV as viable drugs for prostate cancer repurposing, but with a heavy focus on dosing personalization. In silico approaches provide a useful framework for early preclinical evaluation and the optimization of repurposed drugs, supporting the early evaluation of repurposed drug candidates in oncology. Full article

Objectives: Surgical site infections (SSIs) represent a significant postoperative challenge. Although timely perioperative prophylaxis with cephalosporins is essential to prevention, adherence to the recommended 30–60 min administration window may be challenging with traditional intravenous infusion (IVI) in settings with high surgical turnover, as is the case in China. Intravenous push (IVP) has been proposed as a more time-efficient alternative. This scoping review aims to map the available evidence comparing IVP with IVI for perioperative cephalosporin administration across four domains: safety, pharmacokinetics/pharmacodynamics (PK/PD), efficacy, and economic impact. Methods: A systematic search was conducted across PubMed, Embase, Web of Science, the Cochrane Library, and gray literature up to February 2026. Data were systematically charted and extracted using a standardized form. Results: Of the 14 included sources, only 3 were peer-reviewed comparative studies; the remaining 11 (78.6%) were gray literature documents. Among the gray literature, 72.7% (8/11) permitted or recommended IVP for cephalosporin prophylaxis; however, this proportion reflected practice patterns of heterogeneous methodological rigor. The 3 peer-reviewed studies focused on the safety, PK/PD, and economic outcomes. Two studies—in orthopedic and bariatric surgery, respectively—found no significant difference in adverse event rates between IVP and IVI, though both were limited by small samples. A single small study suggested similar PK/PD target attainment between IVI and IVP cefazolin. No study directly compared SSI rates between the two routes. One study suggested potential cost savings with IVP, but the evidence was dated and based on limited patient numbers. Conclusions: The available evidence for IVP is predominantly derived from gray literature, while peer-reviewed articles suggest that safety and PK/PD profiles do not differ markedly from IVI in the limited populations, surgical procedures, and agents studied; economic data are suggestive but dated. Direct comparative data on clinical efficacy outcomes, such as SSI rates, are absent. Well-powered, multi-center comparative studies comparing IVP and IVI with SSI as a primary endpoint are needed. Full article

Background/Objectives: Adalimumab (ADM) is a recombinant, fully human monoclonal antibody that exhibits pronounced inter- and intra-individual pharmacokinetic variability attributed to several factors. This study aims to externally evaluate the published ADM population pharmacokinetic models and their potential use in clinical practice, as well as to develop novel population pharmacokinetic model. Methods: Literature search was conducted using PubMed to identify ADM population pharmacokinetic models. Data from 195 patients with Crohn’s disease treated at the University Medical Center “Zvezdara”, Serbia, were used for the external evaluation of previously published models. In addition, the development of the new population pharmacokinetic model incorporated informative priors derived from the best-performing published model. Nonlinear mixed-effects modeling was performed in NONMEM^® (versions 7.6) for both prediction- and simulation-based diagnostics of existing models, as well as for the development of a new model. Results: Eight published pharmacokinetic models of ADM were included in the external evaluation. Although none of the models satisfied both population-level and normalized prediction distribution error (NPDE) diagnostic criteria, individual-level performance was acceptable: median prediction errors (MDPEs) were within ±20% across all studies, and median absolute prediction errors (MDAPEs) were below 30% in most cases (7 of 8 studies). The best-performing model was identified and implemented as a priori information in subsequent model development. A one-compartment model using with first-order absorption and elimination best described the data. The apparent clearance (CL/F) was estimated at 0.334 L/day, while informative priors were used for V/F and the effect of anti-drug antibodies (ADAs) on CL/F. Covariate analysis on CL/F identified C-reactive protein (CRP) and dosing regimen as statistically significant predictors (p < 0.01). Conclusions: The previous pharmacokinetic models of ADM exhibited suboptimal performance in population-level metrics and simulation-based diagnostics, while individual-level metrics showed substantial improvement. The newly developed model of ADM highlights associations among immunogenicity, drug pharmacokinetics, and inflammatory burden. Full article

Breast cancer is among the most commonly diagnosed malignancies in women and remains difficult to treat due to therapy resistance and the adverse effects associated with conventional chemotherapeutic regimens. In this study, the anticancer activity of the ethanolic root extract of Salvadora persica (S. persica), commonly known as Miswak, was evaluated in human breast cancer cells using a combination of in vitro assays, phytochemical profiling, and computational analyses. HRLC-MS/MS characterization revealed a wide range of bioactive constituents, including alkaloids, flavonoid derivatives, glucosinolates, and fatty acid–based molecules detected under both ionization modes. The extract exhibited a concentration-dependent cytotoxic effect on breast cancer MCF-7 and MDA-MB-231 cells, with IC₅₀ values of 144.1 and 176.3 µg/mL, respectively, as determined by the MTT assay, while exerting negligible toxicity toward normal Vero cells. Miswak extract enhanced intracellular ROS production, disruption of MMP, nuclear condensation, and increased apoptotic cell populations, along with S-phase cell cycle arrest, pointing toward activation of mitochondrial-mediated apoptosis. In silico docking results indicated that key phytoconstituents exhibit strong binding interactions with multiple breast cancer–relevant targets such as ERα, PR, EGFR, HER3, IGF-1R, and GPER. Additionally, pharmacokinetic and toxicity predictions suggested favorable drug-like properties with minimal safety concerns. Thus, these findings support its potential as a promising plant-derived therapeutic candidate for breast cancer. Full article

Every year, respiratory syncytial virus (RSV) causes an estimated 33 million lower respiratory tract infections in children under five years of age, driving millions of hospitalizations worldwide and substantial mortality in developing countries. For 28 years, the monoclonal antibody (mAb) palivizumab has been the principal agent for RSV immunoprophylaxis, reducing hospitalization in defined high-risk groups through monthly intramuscular dosing. The recent approval of two second-generation long-acting mAbs, nirsevimab and clesrovimab, and maternal preF vaccine has fundamentally changed the RSV prevention landscape. In contrast to palivizumab, the long-acting mAbs offer single-dose seasonal protection across a broader infant population, enabling universal immunization programmes for the first time. In this review, we conjointly examine nirsevimab and clesrovimab across their mechanisms of action, pharmacokinetics, efficacy, safety and cost-effectiveness, using palivizumab as the reference standard. Cross-trial efficacy comparisons are complicated by differences in study populations and endpoint definitions; however, when these factors are considered, the available evidence suggests that all three agents offer broadly comparable protection against severe RSV disease. All three agents also demonstrate favourable and comparable tolerability profiles. Nirsevimab is now supported by a substantial body of real-world evidence confirming effectiveness in routine immunization programmes that closely align with registrational studies. Clesrovimab, as the newest agent, currently lacks real-world effectiveness, and both long-acting monoclonals require further confirmatory evidence in high-risk groups. Overall, existing data support that both monoclonals have equivalent efficacy and safety profiles as palivizumab, and choice should be based on cost-effectiveness and local availability, with consideration given to optimal integration of infant immunoprophylaxis alongside maternal RSV vaccination programmes. Full article