Search Results (7,096)

LY104 (previously designated as B7) is a selective phosphodiesterase 4 inhibitor with promising activity against chronic obstructive pulmonary disease. We previously reported its single-dose pharmacokinetics and tissue distribution in rats. In the present study, a liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed and validated for the simultaneous quantification of LY104 and its major metabolite M1 in rat plasma following ICH M10 guidelines. The method showed excellent linearity over 20–1200 ng/mL for both analytes, with retention times of 2.85 min (LY104) and 3.22 min (M1). Using this method, we extended our previous work in several directions. Re-analysis of previously published single-dose pharmacokinetic and tissue distribution data revealed no significant sex differences for LY104. Newly generated multiple-dose studies (1 mg/kg daily for 7 days) demonstrated no accumulation of LY104 or M1. The pharmacokinetic profile of M1 was quantified for the first time. Comprehensive in vitro investigations included plasma and liver microsomal stability, plasma protein binding, and excretion studies. This systematic preclinical pharmacokinetic characterization of LY104 and M1, incorporating re-analysis of existing data with sex stratification, newly generated multiple-dose and metabolite data, excretion studies, and comprehensive in vitro investigations, provides useful information to support further drug development and clinical trial design. Full article

The immune response is essential in the protection of our body against pathogens; however, the inflammatory response caused by the immune system can become a disease itself. In fact, anti-inflammatory and immune-suppressive drugs are applied to limit the immune response to treat inflammatory diseases. Flavonoids are plant-derived polyphenols extensively investigated for their anti-inflammatory and antioxidant properties in inflammatory diseases. Studies applying isolated compounds as well as using supplements as nutraceuticals based on flavonoids have been conducted. Our review systematically analyzed the top five studied flavonoids between 2020 and 2025: quercetin (1742 articles), kaempferol (642), luteolin (589), apigenin (419), and epicatechin (354), highlighting their major therapeutic applications in diseases affecting the liver (12%), nervous system (11%), and lungs (10%). Mechanistically, these compounds act as multi-target agents mainly by inhibiting NF-κB and inducing Nrf2-dependent antioxidant programs. Application of advanced delivery systems, which increase oral bioavailability by up to 20-fold, overcomes pharmacokinetic bottlenecks. Clinical highlights demonstrated promising therapeutic effects, including reduced intrahepatic lipid accumulation in non-alcoholic fatty liver disease patients following quercetin supplementation (11.5% to 9.6%) and accelerated SARS-CoV-2 clearance after quercetin phytosome administration. The translation of flavonoids into standardized clinical therapies remains limited by the lack of large-scale, well-controlled clinical trials. Full article

Background/Objectives: Several novel biologics and small-molecule therapies have emerged for the treatment of antihistamine-refractory chronic spontaneous urticaria (CSU), yet no study has directly compared their speed of response. This study aims to provide indirect evidence on the relative time to meaningful clinical response across approved and investigational therapies using a Bayesian network meta-analysis. Methods: Phase 2 and phase 3 randomized controlled trials reporting UAS7 scores in a graphical format for antihistamine-refractory CSU were included. The primary outcome was the mean time in weeks to minimal clinically important difference (MCID), defined as a UAS7 reduction of 10 points. Data were extracted using WebPlotDigitizer (v4.7) and analyzed via Bayesian random-effects network meta-analysis in MetaInsight (v6.4.0), with placebo as the reference node. Results: All drugs except rilzabrutinib 400 mg daily demonstrated faster mean time to MCID than placebo. Fenebrutinib had the fastest mean time to MCID (0.67–0.76 weeks), and tezepelumab the slowest (5.41–5.65 weeks). Only omalizumab 300 mg every 4 weeks, dupilumab 300 mg every 2 weeks, and ligelizumab 72 mg and 120 mg every 4 weeks achieved statistically significant reductions compared with placebo. All treatments had wide credible intervals reflecting limited direct comparisons. Conclusions: This is the first network meta-analysis comparing time to meaningful symptom control across therapies for antihistamine-refractory CSU. Omalizumab, dupilumab, and ligelizumab demonstrated statistically significant reductions in time to MCID compared with placebo. Head-to-head trials with standardized outcome reporting would enable more definitive comparative conclusions. Full article

Background/Objectives: Sensorineural hearing loss (SNHL) is a chronic condition with no established pharmacological treatment. Recent advances in drug-based therapies offer promising opportunities to prevent or treat SNHL. This scoping review summarizes the current landscape of pharmacotherapeutics for SNHL. Methods: This scoping review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR). A literature search of PubMed, Google Scholar, Embase, Scopus, and Web of Science was conducted in 2024 using keywords related to SNHL and pharmacotherapeutics. A review protocol was preregistered on the Open Science Framework. A systematic search of five electronic databases identified published studies from 2004 to 2024 on pharmacological treatments for SNHL in human participants, as well as ongoing clinical trials. Interventions were categorized by mechanism of action: antioxidant therapy, steroid-based combination therapy, hematologic-based therapy, pathway modulator therapy, regenerative therapy, and gene therapy. A narrative synthesis approach was used to map key trends across treatment types, study designs, and outcomes. Results: Sixty-six records met the inclusion criteria, including 48 published studies and 18 ongoing or recently completed clinical trial records. Antioxidants, corticosteroids, hematologic agents, and pathway modulators have demonstrated potential in preventing or treating SNHL caused by cisplatin, aminoglycosides, noise-induced ototoxicity, and intraoperative cochlear implantation trauma. Emerging regenerative and gene therapies show promise as future pharmacologic treatment options. Conclusions: Pharmacologic therapies for SNHL are promising but remain constrained by small sample sizes, heterogeneous study designs, and drug delivery challenges across the blood–labyrinth barrier. Future research should prioritize multicenter randomized trials, optimized delivery strategies, and integration of precision medicine approaches. Full article

Atrial fibrillation (AF) is the most common tachyarrhythmia worldwide. Accompanying the increasing age of the general population, as well as an increase in underlying cardiovascular disease in the United States, is an explosive rise in the incidence and prevalence of this condition. We reviewed observational cohort studies, systematic reviews, meta-analyses, and randomized controlled trials (RCTs) to determine both underlying risk factors and treatment of AF, with particular focus on comorbid conditions influencing treatment success. Numerous studies have demonstrated a reciprocal relationship between maladaptive cardiac remodeling and AF, with the suggestion that aggressive management of both AF itself and resultant cardiovascular disease can lead to reversal of both conditions. Ultimately, many modifiable risk factors for AF exist, with treatment delays associated with a shift towards these conditions becoming unmodifiable. While a large area of focus for AF research has been on determining the optimal pharmacological strategy (i.e., rate versus rhythm control), results have been mixed, with emerging guidelines now pointing towards a flexible treatment strategy that allows for consideration of patient comorbid conditions, medication ease and affordability, and patient preference. Treatment of AF also includes prevention of thromboembolic events. In recent years, novel strategies for surgical or physical occlusion of the left atrial appendage (LAA) with devices such as the Watchman have arisen. Multiple large RCTs have demonstrated the safety and efficacy of these devices, but consideration must be given towards the patient’s bleeding risk, as short-term courses of blood thinners are still considered the standard of care. Finally, emerging therapies for AF include novel drug combinations, neuromodulation devices, and potentially glucagon-like peptide receptor-1 (GLP-1) agonist medications for reduction in overall metabolic disease. Full article

Cancer represents one of the major public health issues in sub-Saharan Africa (SSA), with increasing incidence and mortality rates as a result of late diagnosis, limited healthcare infrastructure, and financial difficulties. Traditional medicine plays an important role in healthcare across different populations in SSA, as more than 80% of the population depend on indigenous plant-based remedies for treating or managing different ailments, including cancer. This study aimed to document medicinal plants traditionally used to treat cancer in SSA. A systematic search of all documents available in the last two decades (2006–2026) was conducted using PubMed, Web of Science, and Google Scholar databases. After screening studies using the predefined inclusion and exclusion criteria, 55 studies met the eligibility requirements and were selected for analysis based on their relevance to the topic, geographic scope, and reported applications in cancer management. The scientific names of the identified plant species and their taxonomic authorities were verified using the Plants of the World Online database. A total of 556 species, belonging to 110 families, were recorded as medicinal plants used to treat various forms of cancer in SSA. The top five families with the most frequently used plants were Fabaceae (51 species), Asteraceae (34 species), Euphorbiaceae (25 species), Apocynaceae (22 species) and Lamiaceae (22 species). Frequently cited plants include Kigelia africana, Annona muricata, Adansonia digitata, Carica papaya, and Tamarindus indica. A total of 11 plant parts were documented, with leaves (41.20%), roots (18.75%), and bark (17.25%) being the dominant plant parts utilised. The primary methods of preparation were decoction (38.23%), powdering and grinding (14.51%), and infusion and tea preparation (49.73%), while the main modes of administration were oral (66.88%) and topical (26.46%). The results show that traditional medicinal plants hold significant potential as sources of novel anticancer drugs in SSA. However, a significant gap exists between ethnobotanical knowledge, laboratory research, and clinical application. Rigorous pharmacological and toxicity evaluations and well-designed clinical trials on the identified medicinal plants are needed to integrate effective and safe plant-based therapies into evidence-based oncology. Full article

Background: Debate continues to swirl around the effectiveness of novel nicotine-delivery products such as snus and e-cigarettes as tobacco cessation aids. The purpose of this review is to quantify the state of research on modern products, including e-products, and established or developing pharmaceuticals on assisting nicotine users in achieving cessation. Methods: This study relied on a comprehensive assessment of research articles, clinical trials, drug approvals, and textbook material available via PubMed, Ovid Wolters Kluwer, and Wiley. We utilized Python 3.14.2, Anaconda3, the ShinyWeb App, and Py.Litstudy to investigate the selected literature. Our key study elements are product evolution and cessation behavior associated with e-cigarettes, snus, nicotine gum, nicotine dermal patches, bupropion, varenicline, and cytisine. Results: This manuscript assessed 144 manuscripts published between 1952 and 2025. E-cigarettes and snus, while containing some limited cessation benefit, were not identified to be effective enough at attaining cessation (when used exclusively) to be prescribed as cessation tools. Cytisine was identified as having very similar cessation outcomes to established pharmaceuticals such as varenicline. Conclusions: Since their iteration, e-cigarettes and snus products were marketed as cessation aids. This review found that there is scant evidence to support that modern snus and e-cigarette products work as cessation aids when used in exclusion of other more traditional approaches to cessative aid. Additionally, more modern pharmaceuticals such as cytisine may have benefit as solo cessation tools over novel nicotine-delivery products. Full article

Postoperative delirium (POD) is an acute, reversible neurocognitive disorder characterized by confusion and altered consciousness. With the improvement in research methodologies and the introduction of innovative clinical drugs in recent years, a growing number of randomized controlled trials have been conducted. This article aims to conduct a comprehensive review of the efficacy of general anesthetics—including propofol, ciprofol, sevoflurane, ketamine, esketamine, dexmedetomidine, benzodiazepines, opioids, and lidocaine—in preventing and managing POD, based on randomized controlled trials published in the past five years. Propofol has advantages in preventing POD in pediatric patients. However, its efficacy compared with inhalational anesthetics still requires individualized evaluation in elderly patients. The novel drugs ciprofol and remimazolam exhibit favorable safety profiles and do not increase the risk of POD. The efficacy of dexmedetomidine shows variability across patient populations and surgical types. In addition, specific opioid drugs and lidocaine also demonstrate preventive potential when administered in a standardized manner. Full article

Patient-derived organoids (PDOs) provide ex vivo functional models that capture tumor drug-response patterns across multiple cancer types. Organoid drug sensitivity testing (ODST) has accumulated supportive evidence in single-tumor studies, yet it lacks a pan-cancer biostatistical framework that can support multi-cancer clinical decision-making. This article presents a pan-cancer ODST validation framework that integrates evidence synthesis, regulatory mapping, and adaptive trial design. The framework specifies analytical-performance standards, a three-stage validation architecture, and an explicit cross-tumor portability coefficient that quantifies the transferability of validated evidence among cancer types. Implementation barriers, including heterogeneous tissue-collection standards, variable establishment success, immunotherapy modeling limitations, and regulatory misalignment, are identified, and corresponding mitigation strategies are described. The framework supports a structured pathway from analytical validity to clinical utility for ODST across solid-tumor indications. Full article

Autophagy is an essential mechanism through which cells break down and reuse intracellular proteins and organelles to preserve cellular homeostasis. Under physiological conditions, autophagy primarily exerts a cytoprotective effect; however, aberrant activation or deficiency of autophagy pathways can disturb cellular balance and even trigger apoptosis, thereby contributing to the occurrence and progression of multiple diseases. Flavonoids are natural bioactive components widely distributed in plants, characterized by distinct benefits of synergistic regulation via multiple targets and pathways. This review summarizes the primary mechanisms of flavonoids, focusing on their potential underlying mechanisms against various diseases—including atherosclerosis, cardiovascular diseases, liver diseases, lung diseases, Parkinson’s disease, leukemia, and malignant tumors—via regulating autophagy (including selective autophagy), and sorts out the latest advances in related experimental research over the past five years. In conclusion, flavonoids can effectively ameliorate the pathological processes of multiple diseases by modulating autophagy pathways with favorable biosafety. Nevertheless, low bioavailability remains the core bottleneck restricting their clinical translation. Further optimization of pharmaceutical formulations is warranted to enhance their uptake efficacy in vivo, and rigorous clinical trials are needed to assess their prolonged effectiveness and potential drug interactions, so as to offer new feasible approaches and research directions for the prophylaxis and therapy of various diseases. Full article

Background: Twin-screw wet granulation (TSWG) is a promising continuous manufacturing technology, featuring high operational flexibility, short residence time and consistent quality. The process development of TSWG relies on the synergy of material characterization, screw configuration, and process parameter optimization. Objective: In order to fully combine various design variables, and to accelerate the process development of TSWG, a material–process–equipment integrated design (MPEID) methodology is first applied to the TSWG process of Guizhi Fuling capsule, a botanical drug product. Methods: First, an equivalent formulation was designed to save trial costs. Second, 3D printing technology was used to customize both conveying and kneading elements with the lead, with the kneading discs stagger angle (SA) and the thickness (thick) as screw element variables. The position of fabricated kneading elements was varied to generate different screw configurations. Then, the critical screw parameters (CSPs) and critical process parameters (CPPs) were identified by a two-step design of experiment (DOE) toward optimizing granule quality. Results: As a result, the SA and thick were identified as CSPs, and the liquid-to-solid ratio was the CPP. Under the optimal TSWG process conditions, the twin-screw granulator could be operated under low torque (i.e., average torque = 1.48 ± 0.06 Nm). The dried granules exhibited superior flowability, as well as highly consistent particle size distribution with industrial batches. After capsule filling, the dissolution test results showed the prepared Guizhi Fuling capsules reached 93.7% cumulative dissolution at 15 min, which approached that of commercial capsules (i.e., 93.0%). Conclusions: This study demonstrated the feasibility of proposed MPEID methodology, supporting the efficient and cost-effective process development of TSWG. Full article

Statins are widely used to inhibit cholesterol synthesis and help prevent cardiovascular diseases associated with elevated blood cholesterol levels. Several clinical trials have shown that some of the benefits observed with statins are independent of cholesterol lowering. Part of these pleiotropic effects is related to the ability of statins to directly interact with and alter the physical properties of lipid membranes such as lipid packing and, consequently, membrane fluidity. Membrane lipid therapy is an innovative approach based on the use of drugs with the potential to change membrane lipid structure for therapeutic purposes, including enhancing the intracellular delivery of chemotherapeutic drugs. Evidence from studies using both artificial model membranes and biological membranes supports the potential use of statins as effective drug candidates for membrane lipid therapy. However, the transition from the promising in vitro results to the clinical practice has encountered significant challenges. This commentary highlights the pitfalls in repurposing statins as membrane-modifying agents. Full article

Drug repurposing is often promoted as a faster, lower-risk alternative to de novo discovery, yet substantial barriers continue to limit successful implementation. We performed a scoping review of articles included in PubMed and ScienceDirect with the aim to identify and categorize challenges and analyze the intersections between them. Our review included 73 articles which revealed scientific, clinical, regulatory, economic, and implementation barriers, with the principal being the clinical translation of generated candidates. Scientific challenges include the necessity for new Phase II/III trials to validate efficacy, safety, and optimal dosing in new therapeutic contexts. Across disease areas, domain-specific barriers include subgroup-dependent responses in oncology, resistance and penetration challenges in anti-infectives, and data scarcity in rare diseases. Computational and AI-assisted approaches face fragmented data, model robustness, and insufficient validation. In addition, off-patent drugs face evidence requirements as rigorous as those for de novo entities, yet lack the market exclusivity incentives required to attract private investment. Additionally, an “institutional bottleneck” hinders academic researchers from bringing findings “on-label” due to a lack of regulatory infrastructure and collaborative frameworks. We conclude that drug repurposing requires a distinct translational paradigm involving multi-stakeholder collaboration and early regulatory engagement to bridge the gap between laboratory discovery and patient access. Full article

Background: Hospital-acquired infections (HAIs) represent the most significant complications in patients hospitalized for severe burn injuries, after the immediate post-burn resuscitation phase, and are associated with substantial morbidity and mortality. Methods: This is a narrative review. Evidence was extracted mainly with an in-depth search of MEDLINE, focusing on guidelines, randomized controlled trials, and relevant observational studies published in the last 25 years. The reference lists of the most relevant publications were screened to retrieve additional relevant information. Results: Wound infections, bloodstream infections, pneumonia, and urinary tract infections account for the majority of infectious complications. Their diagnosis can be challenging, particularly in the context of wound infections and sepsis. Burn severity and the resulting disruption of tissue and organ homeostasis can alter the pharmacokinetic and pharmacodynamic (PK/PD) properties of antibiotics, rendering standard dosing and administration strategies inadequate. Higher doses, prolonged or continuous infusions, and therapeutic drug monitoring may be required to optimize antibiotic exposure. The emergence of multidrug-resistant (MDR) pathogens (particularly MDR Gram-negative bacilli) has been widely reported across diverse epidemiological settings and occurs frequently in patients with prolonged hospitalization, further complicating treatment. As a result, the use of broad-spectrum antibiotics is substantial, both for empirical therapy and for targeted treatment. Although antimicrobial stewardship programs can promote more appropriate antibiotic use, evidence on how to effectively implement these strategies in Burn Intensive Care Units remains limited. Conclusions: HAIs in burn patients represent a highly complex clinical scenario. Clinical severity is often significant, diagnosis can be challenging, and MDR pathogens are very prevalent, with high consumption of broad-spectrum antibiotics. Moreover, PK/PD properties of antibiotics can be altered. Antimicrobial stewardship can promote appropriate antimicrobial use, but implementation in this setting has not been adequately studied. Close multidisciplinary collaboration between burn specialists and infectious diseases physicians is essential to ensure effective patient management. Full article

Background and Objectives: Muscle symptoms are the most visible adverse event attributed to statins, but terminology is often imprecise. Most patients report myalgia or nonspecific aches, whereas objective myopathy, inflammatory or necrotizing myositis, rhabdomyolysis, and anti-HMGCR immune-mediated necrotizing myopathy are uncommon and clinically distinct entities. To provide a clinically oriented narrative synthesis of statin-associated muscle symptoms (SAMS) and severe statin-associated myotoxicity, and to propose a practical prevention, evaluation, and management algorithm. The classification of muscle events is used to standardize terminology and avoid diagnostic confusion, not to create a new formal taxonomy. Materials and Methods: A clinically oriented narrative review was performed using PubMed, Google Scholar, and major society documents published from January 2021 to April 2026. Eligible sources addressed SAMS, statin myopathy/myositis, rhabdomyolysis, anti-HMGCR immune-mediated necrotizing myopathy, nocebo/drucebo effects, pharmacogenetics, drug interactions, diagnosis, or management. The final evidence set comprised 55 verifiable sources, including blinded randomized or n-of-1/crossover evidence; meta-analyses; clinical statements and reviews; pharmacovigilance analyses; pharmacogenetic guidance; mechanism-focused reviews; anti-HMGCR series; and lipid-lowering guideline/treatment studies. Because the review was narrative, no pooled estimate or formal PRISMA screening log was generated. Results: Blinded evidence indicates only a small absolute excess of muscle pain with statins, concentrated mainly in the first year of therapy, and that most muscle symptoms reported during statin therapy are not pharmacologically caused by the statin. N-of-1 and crossover trials show that symptom intensity is often similar during statin and placebo periods, consistent with an important nocebo/drucebo contribution. Severe muscle toxicity can nevertheless occur, especially when systemic statin exposure is increased by a high dose, interacting drugs, frailty, renal or hepatic impairment, hypothyroidism, transporter or metabolic genotypes, or intense unaccustomed exercise. Statin choice matters chiefly through dose, pharmacokinetics, and interaction burden. Conclusions: SAMS are common as reported clinical problems, but confirmed statin-caused muscle injury is substantially less frequent than routine clinical attribution suggests. Permanent discontinuation should be reserved for carefully assessed cases. A structured approach—baseline risk assessment, selective CK measurement, exclusion of alternative causes, correction of modifiable risks, dechallenge/rechallenge, statin switching, dose reduction, and combination with non-statin therapy—preserves cardiovascular benefit while protecting the rare patient with genuine toxicity. Full article