داروشناسی
مقالهها، منابع و پژوهشهای تازه حوزه داروشناسی
ورود به زیرشاخهنقشه موضوعی
جستوجوی دقیقداروسازی
علوم دارویی، دارودرمانی، ایمنی و فناوری دارو
زیرشاخهها
برای رسیدن به فهرست متمرکزتر، یک مسیر تخصصی را انتخاب کنید.
داروسازی بالینی
مقالهها، منابع و پژوهشهای تازه حوزه داروسازی بالینی
ورود به زیرشاخهفارماسوتیکس و فناوری دارویی
مقالهها، منابع و پژوهشهای تازه حوزه فارماسوتیکس و فناوری دارویی
ورود به زیرشاخهفارماکوگنوزی
مقالهها، منابع و پژوهشهای تازه حوزه فارماکوگنوزی
ورود به زیرشاخهشیمی دارویی
مقالهها، منابع و پژوهشهای تازه حوزه شیمی دارویی
ورود به زیرشاخهسمشناسی
مقالهها، منابع و پژوهشهای تازه حوزه سمشناسی
ورود به زیرشاخهفارماکوویژیلانس
مقالهها، منابع و پژوهشهای تازه حوزه فارماکوویژیلانس
ورود به زیرشاخهاقتصاد دارو
مقالهها، منابع و پژوهشهای تازه حوزه اقتصاد دارو
ورود به زیرشاخهبیوفارماسی و فارماکوکینتیک
مقالهها، منابع و پژوهشهای تازه حوزه بیوفارماسی و فارماکوکینتیک
ورود به زیرشاخهتازهترین رکوردها
شواهد داروسازی
PubMed2027
Decoding Nano-Bio Interactions: Gene Regulatory Networks in Advanced Drug Loading.
Conventional treatments often face challenges such as the limited ability to penetrate the blood-brain barrier (BBB). The Doxorubicin-loaded graphene oxide/magnetite (DOX/GO/Fe3O4) nanocomplex offers a promising platform due to GO's high surface area and pH-sensitive release, and Fe3O4's magnetic properties. This protocol describes the methodology for evaluating the cytotoxicity of free DOX versus the DOX/GO/Fe3O4 nanocomplex in the A-172 glioblastoma cell line, followed by advanced bioinformatics analysis to identify gene networks and indirect pathways that enhance the nanomaterial's biocompatibility. The methodology integrates the MTT assay, real-time PCR for apoptosis genes (Casp3, Bax, and Bcl-2), and advanced analysis, including protein-protein interaction (PPI) networking, clustering, and promoter motif analysis. The analysis indicated that miR-92a-2-5p is a potential therapeutic target for preventing myocardial damage and enhancing biocompatibility. The findings highlight key regulatory pathways that indirectly boost nanodrug biocompatibility through the modulation of secondary components like miRNAs and cellular stress mechanisms.
PubMed2027
Preparation of Mesenchymal Stromal Cells-Derived Extracellular Vesicles as Carriers for Paclitaxel Delivery.
Mesenchymal stromal cells-derived extracellular vesicles (MSCs-EVs) represent innovative tools as a drug delivery system. Here, we described the standardized manufacturing process to prepare MSCs-EVs loaded with the chemotherapeutic drug Paclitaxel (PTX), starting from adipose tissue lipoaspirates of healthy donors.
PubMed2026
Formulation, evaluation and characterization of fexofenadine IR and paracetamol SR multiparticulate drug delivery system.
BACKGROUND: Multiparticulate Drug Delivery (MDD) system are particularly considered as well suited systems for controlling oral preparations that have low risk of dose-dumping. OBJECTIVES: The current research work was aimed to prepare Fexofenadine HCl immediate release (IR) and Paracetamol sustained release (SR) pellets in a single dosage unit for the treatment of Allergic Rhinitis. Extrusion-spheronization was used to fabricate pellets. METHODS: The formulations were analyzed for several parameters, including micromeritic studies, Friability, Weight variation test, Swelling, X-Ray Diffraction (XRD), Fourier Transform Infrared Spectroscopy (FTIR), Scanning Electron Microscopy (SEM), in-vitro release and stability studies. RESULTS: The results showed that the formulated pellets have an excellent flowability (23.01° to 25.23°), bulk density falls in the range of 1.23 g cm -3 to 1.42 g cm -3 , tapped density ranges 1.43 g/cm 3 1.58 g/cm 3 , carr's compressibility index lie between 10.31 % to 15.17 %, Hausner's ratio ranges 1.11 to 1.18 which concluded pellets had good flow properties. Friability was less than 1%; the T6 formulation showed the maximum swelling of 99.28%. No interaction between excipient and drug was found. T6 showed a drug release of 99.08% in 24 hours. CONCLUSION: The research effectively demonstrated that preparing a single-unit dosage form of paracetamol and fexofenadine is a safe, simple and promising technique for SR of Paracetamol, thereby increasing patient compliance by reducing the dosage frequency.
PubMed2026
Improved transcutaneous delivery of cetirizine hydrochloride for the treatment of post-chemotherapy alopecia: Poke and emulgel approach.
BACKGROUND: Chemotherapy-induced alopecia negatively impacts the mental health of cancer patients. Topical minoxidil, a widely recommended drug for hair regrowth, causes scalp irritation and contact dermatitis. Oral minoxidil causes multiple cardiovascular and neurological side effects. Cetirizine hydrochloride, an antihistamine with a better safety profile than minoxidil, may stimulate hair follicle activity by modulating prostaglandin levels. OBJECTIVES: The present study aimed to develop a cetirizine hydrochloride-loaded emulgel and evaluate its potential, in combination with microneedling, for the treatment of chemotherapy-induced alopecia. METHODS: Different emulgel formulations comprising cetirizine HCl, liquid paraffin, carbopol 940, propylene glycol, oleic acid, Tween 20, Span 20 and propylparaben were optimized using central composite design and response surface methodology. Physicochemical evaluation of the prepared emulgel included physical examination, determination of pH, viscosity, spreadability, drug content and stability. Interactions and compatibility among formulation constituents were assessed using In-silico analysis and Fourier transform infrared spectroscopy. In-vitro drug release, ex-vivo permeation and in-vivo hair growth studies were carried out to evaluate the performance efficiency of emulgel. RESULTS: The prepared emulgels exhibited acceptable physicochemical properties and remained stable for 3 months. Constituents were found to be compatible with each other. The optimized formulation F4 released >95% drug at pH 5.5 within 360 minutes. During an ex-vivo study, ~94% of the drug permeated across rat skin within 6 hours following application of emulgel on the microneedle-pretreated skin. In cyclophosphamide-induced alopecia in rats, application of emulgel to microneedle-pierced skin for 15 days promoted hair growth. CONCLUSION: The prepared cetirizine HCl-loaded emulgel and microneedle combination may be a promising approach to treating chemotherapy-induced alopecia.
PubMed2026
PBPK modeling of intravenous/oral acetaminophen in healthy and pregnant individuals.
BACKGROUND: Drug metabolism may be influenced by pregnancy. Use of acetaminophen (APAP) is prevalent among pregnant women, necessitating the development of effective methods for predicting its in-vivo disposition. OBJECTIVES: A whole physiologically based pharmacokinetic model was developed to predict the pharmacokinetic behavior of APAP following oral or intravenous administration in both healthy subjects and pregnant women across different trimesters (first, second, and third trimesters). METHODS: Phoenix WinNonlin 8.4 was used to establish the model, which was verified by literature data and the fold error method. Sensitivity analysis was used to identify the factors most sensitive to the model results. RESULTS: The model was established successfully. The clearance rate and half-life of intravenous APAP increased during pregnancy and the changes were more obvious with the increase of pregnancy trimesters. Theoretically, adjusting the oral and intravenous doses for pregnant women in the third trimester to 1.23 and 1.16 times those administered to healthy individuals may yield a comparable area under the curve in healthy subjects. According to the sensitivity analysis results, the influencing factors were ranked from largest to smallest as follows: activity of sulfatase > activity of glucuronidase > the constant of the gastrointestinal transport rate > activity of CYP450. CONCLUSION: Pregnancy affects the metabolism of APAP and more attention should be paid to pregnant women in clinical medication.
PubMed2026
Perceived Utility of Combining Atypical Long-Acting Injectable Antipsychotics With Psychosocial Interventions: An Exploratory Survey of Mid-Career Psychiatrists in Japan.
AIMS: Although combining long-acting injectable antipsychotics (LAIs) with psychosocial treatments for schizophrenia is important, psychiatrists' attitudes toward this approach remain underexplored. We investigated Japanese psychiatrists' perceptions of combining atypical LAIs with psychosocial interventions. METHODS: An anonymous cross-sectional web-based survey was administered to 1038 mid-career Japanese psychiatrists, of whom 69 provided complete responses. Participants' general attitude toward recommending atypical LAIs was dichotomized as positive or negative/neutral, and they rated on a 4-point scale the usefulness of combining atypical LAIs with five psychosocial interventions: (1) psychosocial treatment (e.g., psychoeducation), (2) day/night care, (3) community care, (4) financial/employment support, and (5) housing support. RESULTS: Thirty-nine respondents held a positive attitude toward recommending atypical LAIs, whereas 30 held a negative/neutral attitude. A positive attitude was significantly associated with perceiving the combination as useful for psychosocial treatment (p = 0.038), financial/employment support (p = 0.015), and housing support (p = 0.041), but not for day/night care (p = 0.090) or community care (p = 0.079). Free-text rationales most commonly cited improved adherence and relapse prevention, enhanced illness insight, and synergistic effects as reasons for valuing the combination. CONCLUSIONS: This exploratory study suggests that mid-career Japanese psychiatrists, particularly those with a favorable attitude toward atypical LAIs, perceive the combination of LAIs with psychosocial support not merely as an adherence tool but as a synergistic strategy promoting broader functional recovery. Because respondents represent a small, predominantly male, self-selected sample, the generalizability of the findings is limited.
PubMed2026
PGR expression as a pharmacogenomic companion biomarker to GENE70-derived genomic risk in ER-positive/HER2-negative breast cancer.
BACKGROUND: The biology of the estrogen receptor-positive (ER+) and human epidermal growth factor receptor 2-negative (HER2-) breast cancers is heterogeneous even when they are categorized by their risk via genomics. Transcriptomic PGR expression reflects endocrine pathway activity and may provide complementary biological information within established GENE70-derived genomic-risk categories. Whether this molecular marker improves the biological interpretation of genomic-risk stratification beyond conventional clinicopathological assessment remains uncertain. OBJECTIVES: The aim of this study was to determine whether transcriptomic PGR expression provides complementary biological and prognostic information within reconstructed GENE70-derived genomic-risk categories and refines the characterization of endocrine-related tumour biology in ER-positive/HER2-negative breast cancer. METHODS: This study analysed publicly available transcriptomic and clinical data from three cohorts: METABRIC (discovery cohort), GSE96058/SCAN-B cohort (validation cohort) and TCGA-BRCA cohort (molecular validation cohort). The GENE70-derived genomic-risk score was reconstructed for each cohort using matched genes. Cox regression, Kaplan-Meier analysis and subgroup comparisons were used to assess relationships between PGR expression, clinicopathologic variables, molecular features and survival outcomes. RESULTS: Across the three independent cohorts, low transcriptomic PGR expression was consistently associated with higher GENE70-derived genomic risk, increased MKI67 expression, reduced ESR1 expression and enrichment of the Luminal B subtype. Survival findings differed between cohorts. In the discovery METABRIC cohort, transcriptomic PGR expression showed heterogeneous associations with survival, particularly within GENE70-derived high-risk subgroups, whereas the external GSE96058/SCAN-B validation cohort demonstrated consistent associations between low PGR expression and poorer overall survival in both the overall ER-positive/HER2-negative population and GENE70-derived high-risk subgroups. CONCLUSION: These findings suggest that transcriptomic PGR provides complementary biological and prognostic information within GENE70-derived genomic-risk categories. However, because treatment response was not evaluated in the present study, the findings should not be interpreted as evidence of predictive or pharmacogenomic utility and prospective studies incorporating treatment-response analyses are required before such applications can be established.
PubMed2026
Limitations of VKORC1 rs9934438 as a Surrogate Marker for Vitamin K Antagonist Dose Adjustment.
VKORC1 genetic variants are major determinants of interindividual variability in vitamin K antagonist (VKA) dose requirements and are incorporated into several pharmacogenetic dosing guidelines. The promoter variant rs9923231 is considered the clinically relevant marker for genotype-guided VKA dosing. However, the intronic variant rs9934438 is sometimes used as a surrogate marker because it is assumed to be in strong linkage disequilibrium with rs9923231. We aimed to assess whether rs9934438 can reliably substitute rs9923231 in clinical practice. We conducted a retrospective, single-centre study including 939 patients who underwent pharmacogenetic testing. Both variants were genotyped using a TaqMan OpenArray custom panel. Concordance between rs9934438 and rs9923231 was evaluated, and the diagnostic performance of rs9934438 for predicting clinically relevant rs9923231 diplotypes was assessed. Although concordance was high overall, rs9934438 misclassified two patients who, according to rs9923231, required a reduced VKA dose, resulting in potential false-negative classifications. These findings indicate that, while rs9934438 provides informative results in most cases, it may fail to identify some patients requiring dose adjustment. Our results highlight the clinical implications of relying on surrogate markers in pharmacogenetic-guided VKA therapy and support the preferential use of rs9923231 to ensure accurate individualized dosing and optimize treatment safety.
PubMed2026
Molecular Design and Anticancer Activities of Small-Molecule BRAF Inhibitors: A Medicinal Chemistry Perspective.
BRAF is a cytoplasmic serine-threonine protein kinase that plays a critical role in the MAPK signaling pathway. BRAF is the only member of the RAF family activated by mutation in human cancers. Many classes of B-Raf small molecule inhibitors have been identified. In this review, we will highlight typical BRAF inhibitors developed during these decades and provide a reference for the exploration of more potential BRAF inhibitors in the future.
PubMed2026
Quantification of Amlexanox in Beagle Dog Plasma by LC-MS/MS and Its Application in a Comparative Pharmacokinetic Study of Conventional and Sustained-Release Tablets.
Amlexanox, a 5H-benzopyranopyridine derivative with emerging therapeutic potential in metabolic and inflammatory diseases, lacks a validated analytical method for pharmacokinetic studies in beagle dogs. A sensitive LC-MS/MS method was developed and validated for amlexanox in beagle dog plasma according to ICH M10 guidelines. Propranolol served as internal standard. Samples were processed by protein precipitation, and separation was achieved on a CAPCELL PAK C18 column using gradient elution with water and acetonitrile (both containing 0.2% formic acid) at 400 μL/min. Detection used positive electrospray ionization with MRM of m/z 299.0 → 281.0 for amlexanox and m/z 260.0 → 116.1 for IS. The method showed good linearity over 40-2000 ng/mL (R2 > 0.99). All validation parameters met acceptance criteria. The method was applied to a three-period fixed-sequence study in beagle dogs (n = 3, male) comparing intravenous injection (1 mg/kg), conventional tablets (75 mg), and sustained-release tablets (150 mg). The sustained-release formulation prolonged Tmax (3.67 vs. 1.00 h) and residence time (two-fold increase in t1/2 and MRT), and improved absolute bioavailability from 25.36% to 33.09% (relative bioavailability: 151.30%). These findings support the clinical development of a sustained-release amlexanox formulation with reduced dosing frequency and improved patient compliance.
PubMed2026
Real-world pharmacoclinical implementation of risdiplam under a national SMA protocol: A hospital pharmacy registry-based case series.
BACKGROUND: Spinal muscular atrophy (SMA) is a rare neuromuscular disorder treated with disease-modifying therapies such as risdiplam. In Spain, its use is regulated by a national pharmacoclinical protocol that requires structured monitoring. OBJECTIVES: To evaluate real-world use, protocol adherence and registry completeness of risdiplam in routine clinical practice. METHODS: A retrospective registry-based case series was conducted including patients with spinal muscular atrophy treated with risdiplam.Variables included age, SMA subtype, SMN2 copy number, diagnostic confirmation, treatment sequence and persistence. Protocol adherence was assessed according to national criteria. RESULTS: Ten patients were included in the study. SMA types II and III predominated, with one presymptomatic case. SMN2 copy number ranged from three to four in documented cases. Protocol adherence was confirmed in 70% of patients, while 30% lacked key eligibility variables. No off-protocol prescribing was identified. Treatment persistence was 100% and 60% of patients had previously received nusinersen. CONCLUSION: Risdiplam was used appropriately in accordance with protocol criteria. Registry incompleteness, rather than clinical deviation, was the main limitation and standardized data capture is essential for real-world evaluation.
PubMed2026
Sex Differences in Prescribing Patterns of Anticholinergics and β3-Adrenoceptor Agonists for Overactive Bladder: A Nationwide Study in Japan, FY2017-FY2024.
OBJECTIVES: Drug treatment for overactive bladder (OAB) is changing, with an increasing share of β3-adrenoceptor agonists relative to anticholinergics, but it is not known how far this change has progressed in older people, who are most vulnerable to the risks of anticholinergics. We examined the use of these drugs in Japan by age and sex, and analyzed changes in anticholinergic burden using a large database. METHODS: We analyzed outpatient prescriptions of two β3-adrenoceptor agonists and six anticholinergics from FY2017 to FY2024, using the sex- and age-stratified tables of the NDB Open Data of Japan. Dispensed tablets were converted into patient-days, and the β3-adrenoceptor agonist share was calculated. Anticholinergic burden was measured as ACB-weighted prescription volume (patient-days multiplied by the anticholinergic cognitive burden score). Because FY2021-FY2022 was a period of nationwide generic supply disruption, FY2018 and FY2024 were used as endpoints when estimating change over time. RESULTS: The β3-adrenoceptor agonist share rose from 36.2% to 64.9%, but anticholinergic use fell only slightly (3.10 × 108 to 2.94 × 108 tablets; -5.0%). In FY2024, the β3-adrenoceptor agonist share was higher in men than in women in every age group, and the difference widened with age (+1.2 percentage points at 50-54 years and +14.2 at ≥ 90 years). ACB-weighted prescription volume was higher in women than in men, and the female-to-male ratio rose with age (1.1 at 65-74 years, 1.6 at 75-84 years, and 2.8 at ≥ 85 years). Between FY2018 and FY2024, prescription volume fell by about 20% at 65-74 and 75-84 years, but the fall was smallest in women aged ≥ 85 years (-11.3%). CONCLUSIONS: The β3-adrenoceptor agonist share for OAB has continued to increase in Japan, but this change appears slower in older women, in whom anticholinergic exposure remains high.
PubMed2026
The 2027 BCPT Perspectives on Studies Involving Natural Products, Traditional Chinese Medicine and Systems Pharmacology.
Natural products, including isolated compounds, complex extracts, traditional medicinal preparations and marine, microbial, fungal and animal-derived materials, remain important sources of therapeutic agents and pharmacological discovery. However, variation in biological source materials, preparation methods, chemical composition and experimental design may compromise reproducibility and interpretation. This guideline presents the requirements of Basic & Clinical Pharmacology & Toxicology for studies involving natural products and their semisynthetic or biotransformed derivatives. It provides recommendations for documenting scientific and ethnopharmacological rationale, taxonomy, authentication, provenance, sustainable and lawful sourcing, extraction, chemical characterisation, dosing, bioactivity, safety and data accessibility. Particular emphasis is placed on studying the preparation actually administered, using pharmacologically relevant concentrations and doses, controlling vehicle effects and assay interference and aligning mechanistic and therapeutic claims with the supporting evidence. Complex mixtures do not necessarily need to be reduced to a single active constituent; however, their composition must be adequately characterised, and claims concerning individual constituents, additivity, synergy or antagonism require experimental substantiation. Computational, network and systems-pharmacology analyses should be transparent and reproducible, with experimental validation of central predictions. These recommendations apply equivalent standards to natural products and other interventions while recognising the additional information required to define complex biological materials and improve overall translational relevance.
PubMed2026
ARMED: an Australian cohort retrospective observational study to understand motivations for switching and clinical outcomes of individuals switching to dolutegravir/lamivudine.
BACKGROUND: Although clinical trials and real-world studies demonstrate the efficacy and tolerability of dolutegravir and lamivudine (DTG + 3TC), Australian real-world evidence remains limited despite differences in access to health care and prescribing context. Here, we present the motivations for switching to DTG/3TC (a fixed-dose, single-tablet regimen) and treatment outcomes. METHODS: We performed a retrospective, observational analysis of individuals with HIV with an undetectable viral load (VL; <50 copies/mL) who switched to DTG/3TC during a 24-month inclusion window from 1 December 2020 to 1 December 2022, in nine Australian clinics. Healthcare providers completed an electronic survey using baseline demographics of people with HIV and other clinical information gathered from participant medical records. Data were collected after December 2023 to allow a 12-month follow-up. Primary endpoints were baseline demographics, clinical characteristics, and motivations for switching to DTG/3TC. Secondary endpoints included virologic outcomes and rates and reasons for DTG/3TC discontinuation. RESULTS: Overall, 276 individuals with HIV who switched to DTG/3TC were included. Most were male (97%) and White (76%), with a median (interquartile range) age of 54 (45-61) years. The most common antiretroviral therapy before DTG/3TC switch was abacavir/dolutegravir/lamivudine (54%). The most common reason for switching to DTG/3TC was clinician preference for two-drug regimen (43%). Most individuals (98%) maintained virologic suppression (VL <50 copies/mL), and none experienced virologic failure. Through Month 12, one (<1%) individual discontinued DTG/3TC. CONCLUSIONS: These real-world data support the use of DTG/3TC as a viable treatment strategy in this Australian population of individuals with HIV.
PubMed2026
Medicinal Chemistry Aspects of Thiazole and Thiazolidine Derivatives as Fundamental Building Blocks to Design New NNRTIs Against HIV-1 Reverse Transcriptase.
The therapy to treat the Human Immunodeficiency virus (HIV) and decrease the viral load has been a challenge since its discovery due to its ability to mutate, escape from drug therapies, and immunologic system. Consequently, the development of new therapies, especially potential molecules that focus on specific viral mechanisms to block viral replication, became a critical challenge in recent decades. The Reverse Transcriptase (RT) is an RNA- and DNA-dependent DNA polymerase enzyme that is responsible for transcribing viral RNA into double-stranded DNA. Non-nucleoside RT Inhibitors perform important role in HIV therapy, and they are responsible for inhibiting RT by blocking its allosteric site, which shows physico-chemical properties such as high hydrophobicity and key amino acid-to-hydrogen bond interactions. For this reason, designing new molecules with innovative heterocycles compatible with these characteristics can provide new potential inhibitors. For example, pentacyclic heterocycles like thiazole and its derivatives like thiazolidinedione, which have physico-chemical properties that can interact with the allosteric site of RT, can be a new perspective in designing new Non-nucleoside RT Inhibitors. This work reviews the scientific literature concerning these compounds and can help the design of new antiviral therapeutics.
PubMed2026
Trophic drivers of lead and cadmium bioaccumulation in waterbird eggshells: a non-invasive assessment at Gandoman Wetland, a Ramsar site in Iran.
Anthropogenic expansion has intensified heavy metal pollution in aquatic ecosystems, posing a severe threat to avian biodiversity. This study utilizes bird eggshells as non-invasive biomarkers to assess lead (Pb) and cadmium (Cd) contamination in the Gandoman Wetland, Iran. During the 2023 breeding season, eggshells were collected from three species with distinct ecological roles: the common tern (Sterna hirundo), the black-necked grebe (Podiceps nigricollis), and the Eurasian coot (Fulica atra). Metal concentrations were determined using an Agilent 240FS AA atomic absorption spectrometer (Agilent Technologies, USA). The results revealed that Pb concentrations consistently exceeded Cd levels across all species, a phenomenon attributed to the ionic mimicry of Pb2+ with Ca2+ during shell mineralization. Notably, mean concentrations for both metals significantly exceeded established hazard thresholds (Pb: 4 mg/kg; Cd: 2 mg/kg) in all species. The common tern, a high-trophic level piscivore, exhibited the highest mean concentrations (Pb: 424.29 mg/kg; Cd: 23.39 mg/kg), while lower concentrations were recorded in the black-necked grebe (Pb: 174.60 mg/kg; Cd: 1.75 mg/kg) and the Eurasian coot (Pb: 44.58 mg/kg; Cd: 2.38 mg/kg). One-way ANOVA confirmed significant interspecific differences (P < 0.05), supporting the trophic level hypothesis of bioaccumulation. Pearson correlation analysis showed nonsignificant relationships between Pb and Cd, suggesting distinct pollution sources, likely industrial effluents for Pb and agricultural runoff for Cd. These findings characterize Gandoman Wetland as a high-risk environment and highlight the urgent necessity for stringent pollution control and management strategies to safeguard wetland-dependent bird populations.
PubMed2026
Advances in Extracellular Vesicle-Based Innovative Drugs Targeting Alzheimer's Disease.
The scarcity of effective therapies for Alzheimer's disease (AD) underscores the urgent need for innovative strategies. This review focuses on the targeted delivery of engineered small extracellular vesicles (sEVs, 30-150 nm). By capitalizing on their intrinsic properties as natural nanocarriers-including low immunogenicity and excellent biocompatibility-these EVs can be engineered to co-deliver therapeutic cargoes such as specific miRNAs, neurotrophic factors (e.g., BDNF), and nucleic acid modalities (e.g., siRNA/ASO targeting BACE1). While a single construct simultaneously delivering all these agents with proven in vivo synergy remains a conceptual framework rather than a validated reality, independent studies have demonstrated that EV-mediated delivery of each cargo type exerts beneficial effects on AD pathology, including Aβ clearance, Tau pathology alleviation, and neuroinflammation suppression. The intranasal administration offers a significant brain-targeting advantage by enabling direct nose-to-brain delivery, bypassing the blood-brain barrier and minimizing peripheral biodistribution. Recently, a phase I/II trial (Ruijin Hospital) demonstrated that intranasal MSC-EVs are safe and produce durable cognitive improvements (ADAS-Cog ↓ 2.33 points at week 12, sustained to - 3.98 points at week 36) in the medium-dose cohort, exceeding the minimal clinically important difference (MCID) of ≥ 2 points for AD. Based on these demonstrated clinical and preclinical evidence, we propose that rationally engineered EVs, following rigorous systematic pharmacology and safety assessments, hold transformative potential to pioneer a safe, efficacious, and non-invasive breakthrough therapy for AD, while acknowledging that critical challenges in GMP manufacturing, biodistribution, and regulatory approval remain to be resolved.
PubMed2026
An overview of international reference values for vitamin E intake - similarities and differences in derivation.
PURPOSE: The scientific knowledge for the essential fat-soluble vitamin E (VitE) remains inconclusive. There is still a lack of valid status parameters and deficiency symptoms for insufficient intake. Therefore, the derivation of a dietary reference value (DRV) for VitE is challenging and differs between the different organizations and countries. The aim of the current paper is to provide an overview of selected international DRVs and discuss the different derivation procedures. METHODS: DRVs from sixteen countries and international organizations were retrieved, compared and evaluated. RESULTS: The DRVs are inconsistent in the absolute value as well as the employed concept of derivation. Due to the uncertainty of the available data some organizations did not specify a DRV. Others used plasma cut off levels or the required amount for the protection of polyunsaturated fatty acids against oxidation. Many DRVs are based on population intake data and given as adequate intake. But this approach may overestimate the VitE needs. CONCLUSION: In conclusion, due to missing symptoms and markers of insufficient supply, the compensation of daily losses with the consideration of the bioavailability appears to be a good basis for deriving a DRV for VitE intake. A balanced and plant-based diet (without supplements) appears to be sufficient for an adequate VitE supply.
PubMed2026
GLP-1R expression and dermatological diseases: a mendelian randomization and real-world study.
BACKGROUND: Although glucagon-like peptide-1 receptor (GLP-1R) is widely expressed in multiple tissues and organs including skin and subcutaneous tissue, with diverse physiological roles in metabolism and immunity, the potential causal association between GLP-1R expression and dermatological diseases remains unclear. METHODS: Available cis-expression quantitative trait loci (cis-eQTLs) were selected as genetic instruments for GLP-1R expression. A two-sample Mendelian randomization (MR) analysis was employed to assess the potential causal association between GLP-1R expression and dermatological diseases. Subsequently, a two-step mediation MR analysis was conducted to explore the mediators between GLP-1R expression and dermatological diseases. Finally, a real-world pharmacovigilance analysis using the Food and Drug Administration Adverse Event Reporting System (FAERS) database was conducted to provide supplementary real-world evidence. RESULTS: Our study revealed distinct associations between GLP-1R expression and dermatological diseases. Specifically, GLP-1R expression was significantly associated with a reduced risk of bullous pemphigoid (OR = 0.47, 95% CI = 0.31-0.72, P < 0.001), as well as an increased risk of psoriasis (OR = 1.19, 95% CI = 1.08-1.32, P < 0.001) and urticaria (OR = 1.41, 95% CI = 1.23-1.61, P < 0.001). Further mediation MR analysis suggested that the immune cell phenotype HLA-DR on B cells might mediate the causal association between GLP-1R expression and bullous pemphigoid, with an estimated mediation proportion of 35.7% (P = 0.003). Other immune cells including Monocytic Myeloid-Derived Suppressor Cells Absolute Count, HLA-DR on CD14 + CD16- monocytes, and HLA-DR on CD14 + monocytes were also identified as potential mediators, with estimated mediation proportions of 23.6% (P = 0.010), 13% (P = 0.024), and 12.7% (P = 0.036), respectively. In the complementary FAERS analysis, consistently, GLP-1RAs reports showed a lower reporting signal for bullous pemphigoid than sodium-glucose cotransporter 2 inhibitors (SGLT2is) reports. CONCLUSION: Our findings suggest that GLP-1R expression is associated with a reduced risk of bullous pemphigoid, which may be partly mediated by specific immune cell phenotypes.
PubMed2026
Insights into Drug Absorption Impairment Mechanisms in Hepatic Impairment using Physiologically-based Pharmacokinetic Modelling: A Case Study with Nilotinib.
Nilotinib is reported to have a reduced maximal drug concentration (Cmax) in patients with hepatic impairment (HI). Given this compound is poorly soluble, highly lipophilic and has a positive food effect, reduced absorption in HI may be due to impaired micelle-mediated solubility resulting from reduced intestinal bile salts. PBPK modelling can be used to test this hypothesis as well as being a diagnostic tool to elucidate other potential mechanisms not captured by the base model. In this study, a mechanistic PBPK model for nilotinib was developed and its performance was evaluated in HI patients. A 'learn-and-confirm' approach was taken, using clinical food effect data to validate the model's mechanistic sensitivity to bile salt-mediated solubility. The final model recovered clinical studies well, with area-under-the-curve (AUC) and Cmax being within 0.8 - 1.25-fold for fasted studies and 1.5-fold for fed/fasted ratios. AUC and Cmax were well recovered in mild HI (within 0.8 - 1.25-fold) and reasonably well recovered in moderate HI (within twofold) but significantly overpredicted in severe HI (> twofold). Bile salt concentrations were reduced across gastrointestinal segments for moderate and severe HI in line with in vitro data. Following twofold and 2.5-fold reductions in bile salts in moderate and severe HI, respectively, sensitivity was minor. Given uncertainty around the fugut, this was reduced to better recover the Cmax (within two-fold). PBPK modelling can be used as a diagnostic tool to evaluate impaired mechanisms in HI.
PubMed2026
Nanocarrier-Enabled Delivery of Glucosinolates for Skin Cancer Prevention and Therapy.
Skin cancer continues to pose a significant global health burden, with conventional therapeutic modalities limited by systemic toxicity, poor tumor selectivity, and the development of therapeutic resistance. Glucosinolates (GLs) and their hydrolyzed product, sulforaphane, have attracted considerable interest as chemopreventive and therapeutic agents owing to their potent antioxidant, anti-inflammatory, and pleiotropic anticancer activities. However, the clinical translation of these phytochemicals is severely hindered by their chemical instability, rapid metabolism, and poor bioavailability. Nanocarrier systems, particularly biodegradable polymeric nanoparticles such as poly(lactic-co-glycolic acid) nanoparticles, offer a promising strategy to overcome these barriers by enhancing compound stability, improving bioavailability, and enabling tumor-targeted delivery via the enhanced permeability and retention effect. This review critically evaluates recent progress in the development of GL and sulforaphane-loaded nanocarriers, detailing their physicochemical properties, in vitro and in vivo anticancer efficacy, and safety profiles, highlighting their potential to advance more effective and less toxic therapeutic strategies for skin cancer prevention and treatment.
PubMed2026
Predicting gallstones risk with body composition analysis and machine learning: a dual-center cohort study.
BACKGROUND: To compare the predictive performance of computed tomography (CT) body composition indices, anthropometric indices, and laboratory indices for gallstones occurrence, and to construct machine-learning models to improve performance. METHODS: The dual-center retrospective cohort enrolled patients who underwent initial abdominal CT between January 2017 and January 2023, had no gallstones detected, and completed at least 3 years of follow-up. The data analysis was performed in April 2026. They were divided into gallstone group and non‑gallstone group by follow‑up findings. A deep-learning tool, Body and Organ Analysis (BOA), was used to quantify fat, muscle, and bone at the level of the third lumbar vertebra. The area under the receiver operating characteristic curve (AUC) of these indices was compared with that of anthropometric and laboratory indices. Predictive models were developed in the training cohort. Model performance was evaluated using fivefold cross-validation and an independent test cohort. RESULTS: 1,944 patients were evaluated, including 1,437 in the training cohort (Center 1; median age, 63 years [25th-75th percentile, 55-72]; 699 males) and 507 in the test cohort (Center 2; median age, 63 years [55-71]; 266 males). In univariate analysis, neutrophil-to-lymphocyte ratio (NLR) showed the highest AUC (0.627, 95% confidence interval [CI]: 0.586-0.668). The extreme trees (ET) model performed best, with a test-set AUC of 0.772 (95% CI: 0.714-0.822). SHapley Additive exPlanations (SHAP) analysis identified the area ratio of subcutaneous to total fat as the most important feature. CONCLUSIONS: NLR was the best single predictor but had limited standalone utility. Among models integrating the three indicator categories, the ET performed best.
PubMed2026
Shedding light on amphipod behaviour: Baseline locomotion behaviour for laboratory ecotoxicology experiments.
Behavioural endpoints offer a sensitive, non-invasive alternative to traditional mortality assays. Yet, they remain underutilized in regulatory frameworks due to a lack of standardised methodologies and baseline behavioural data. This study investigates the baseline locomotion of the marine amphipod Marinogammarus marinus to external light triggers to support standardised laboratory behavioural assays. Using an automated observation chamber, here we tracked swimming behaviour in response to light stimuli, quantifying locomotion as distance travelled. Groups of eight amphipods were tested in large crystalizing dishes over four days in an 8-minute trial involving two light exposures. A total of 60 individuals - males, females, and brooding females - were assessed. Light consistently triggered activity, with males showing strong negative phototaxis and brooding females the weakest. A startle response was observed within 3-5 seconds of initial light exposure, though responses diminished with repetition, suggesting potential overstimulation or habituation. Inter-individual and day-to-day variability highlighted the need for repeated measures. Additional trials with 32 males evaluated the effects of experimental conditions. Wall-hugging (thigmotaxis) appeared to be an escape response, not anxiety-related. Notable decreases in dissolved oxygen and pH within 24 hours were attributed to the amphipods' presence rather than activity, while salinity fluctuations due to evaporation did not visibly affect behaviour. Differences between male groups from the two separate experiments suggest behavioural shifts due to seasonal variation. This study establishes baseline behavioural data for M. marinus and demonstrates the value of automated tracking systems in behavioural assays in laboratory settings. It emphasizes the need to account for sex, size, and temporal variation in assay design and supports integrating behavioural endpoints into regulatory protocols.
PubMed2026
Stimuli-Responsive Hydrogel Systems for Breast Cancer Therapy: Advances in Targeted Delivery and Tumor Microenvironment Modulation.
Breast cancer (BC) stands as a major medical concern for women because treatment hurdles include drug resistance combined with treatment failure and severe side effects and the intricate tumor microenvironment (TME). The treatment-resistant breast cancer subtype triple-negative breast cancer (TNBC) exhibits high aggressiveness through its failure to respond to targeted treatment yet maintains substantial metastatic potential. Hydrogels that react to stimuli have recently shown promise as solutions for solving these clinical issues. These hydrogels show response to precise stimuli which include pH, temperature and light and magnetic fields and biological elements including glutathione together with overexpressed enzymes MMP2 and MMP9 that appear within BC tumors. Hydrogel systems that respond to enzymes release drugs precisely at tumors thus minimizing drug side effects and optimizing their therapeutic effects. Hydrogel systems become more effective because of their ability to control drug delivery and combine various treatments when nanomaterials are incorporated as parts of their structure. Hydrogels must have adequate mechanical toughness because it enables them to withstand physical pressure without losing their drug release capabilities throughout the extended treatment period. This review has demonstrated that hydrogel-based drug delivery systems decrease tumor dimensions while inhibiting metastasis making them an advanced treatment strategy for BC management. The novel hydrogel platforms will lead to individualized treatment methods which show substantial promise to enhance breast cancer therapy results.
PubMed2026
Antibiotic prescribing that aligns with a host-protein test at US acute care settings is associated with fewer subsequent hospitalisations.
BACKGROUND: Differentiating bacterial from viral infections in acute care is challenging, often leading to inappropriate antibiotic use. MeMed BV (MMBV) is a host-protein test integrating TNF-related apoptosis-inducing ligand, induced protein-10 and C-reactive protein to distinguish infection aetiology. We evaluated whether alignment between MMBV results and antibiotic prescribing is associated with downstream clinical outcomes and costs. METHODS: Data were pooled from two prospective US studies (APOLLO and JUNO). Alignment was defined as: antibiotics prescribed for bacterial MMBV results or no antibiotics for viral results. The primary outcome was unplanned revisits and hospitalisations within 28 days. Exploratory analysis estimated healthcare costs using 2024 Healthcare Cost and Utilisation Project data. RESULTS: The cohort included 297 adults (median age 36.4 years). 20.5% had bacterial, 68.0% viral and 11.4% equivocal MMBV results. In patients with bacterial MMBV results, antibiotic prescription (alignment) was significantly associated with fewer revisits (5.0% vs 33.3%; p=0.003) and hospitalisations (2.5% vs 19.0%; p=0.026). For patients with viral results, outcomes were comparable regardless of antibiotic use. In the exploratory analysis, alignment with MMBV was associated with lower estimated costs (£101 vs £1175/patient; difference £1074), driven mainly by fewer hospital days in the aligned group. CONCLUSION: Misalignment between MMBV bacterial results and antibiotic prescribing in acute care settings was associated with higher revisit and hospitalisation rates. These findings identify a quality gap under diagnostic uncertainty and support a methodology which includes assessment of test versus clinical outcome alignment when evaluating new diagnostic tests.
PubMed2026
Comparative genomic analysis of Rahnella sp. PAMC25617 isolated from cryoconite reveals a glutathione-dependent formaldehyde detoxification pathway.
Rahnella species are environmentally versatile bacteria widely distributed in terrestrial and aquatic ecosystems; however, the genomic basis of formaldehyde detoxification and stress adaptation in cryoconite-associated Rahnella remains poorly understood. In this study, we performed phylogenomic, comparative genomic, pan-genomic, stress-response, and functional analyses of Rahnella sp. PAMC25617 isolated from polar cryoconite to investigate glutathione (GSH)-dependent formaldehyde detoxification and its evolutionary conservation. Genome-based phylogeny, average nucleotide identity (ANI), and digital DNA-DNA hybridization (dDDH) analyses demonstrated that PAMC25617 represents a distinct genomic lineage within the genus Rahnella. The draft genome comprised 5.33 Mb with a GC content of 52% and encoded multiple genes associated with formaldehyde detoxification and one-carbon metabolism, including frmA, yeiG, yeiP, yeiR, and a putative formate dehydrogenase gene cluster. Comparative genomic analyses further showed that these detoxification genes were consistently associated with GSH transport (gsiA-D), redox-associated (frdA-D), and regulatory (fnr) genes, suggesting coordinated roles in detoxification and redox homeostasis. Comparative stress-response gene profiling across 121 Rahnella genomes further revealed widespread conservation of oxidative stress defense systems, including oxidoreductases, aldehyde dehydrogenases, GSH-associated enzymes, thioredoxin, catalase, and molecular chaperones. Notably, PAMC25617 possessed an enriched repertoire of oxidative stress and detoxification-related genes, indicating enhanced stress adaptation potential in cold and chemically challenging environments. Pan-genome analysis indicated a highly diverse and open pan-genome structure with a low Heap's law exponent (γ = 0.336), reflecting ongoing genome diversification and ecological adaptation. Multiple sequence alignment (MSA) further demonstrated strong conservation of catalytic motifs and active-site residues in FrmA and YeiG among phylogenetically diverse bacteria. Physiological assays showed that PAMC25617 exhibited tolerance to formaldehyde stress under liquid culture conditions. These findings suggest that R. sp. PAMC25617 employs an integrated GSH-dependent detoxification and oxidative stress response system that may facilitate survival and adaptation in extreme polar environments.
PubMed2026
Extent of Digital Health Fragmentation and Potential Implications for Antimicrobial Prescribing: Rapid Evidence Review.
BACKGROUND: Prior microbiology results, resistance patterns, and antimicrobial exposure are central to safe and effective antimicrobial prescribing. Digital health fragmentation refers to the dispersal of patient data across multiple electronic systems and the associated challenge of accessing complete information at the point of care. Antimicrobial prescribing for infections represents a critical use case to investigate the impact of digital health fragmentation on patient care. While interoperability has been studied in the context of patient safety, no review has described digital health fragmentation within the United Kingdom and examined its impact on antimicrobial prescribing and antimicrobial stewardship (AMS). OBJECTIVE: This study aimed to (1) characterize the extent of digital health fragmentation in the United Kingdom, (2) summarize the available evidence on its impact on AMS and prescribing practices in high-income countries, and (3) identify potential solutions. METHODS: A rapid review of the peer-reviewed literature was conducted following published guidance for rapid reviews and the PRISMA (Preferred Reporting Items of Systematic Reviews and Meta-Analyses) statement. MEDLINE ALL and PsycInfo were searched on August 19, 2025, using search terms relating to digital health fragmentation or interoperability, patient safety, and antimicrobial use. Searches were limited to English-language publications from 2015 (for characterizing the recent trends or current state of digital health fragmentation in the United Kingdom) or 2010 onward (for AMS-related impacts and solutions). Screening was conducted by 4 researchers following predefined inclusion and exclusion criteria. Extracted data were synthesized narratively through framework analysis. Study quality was appraised using the Mixed Methods Appraisal Tool. RESULTS: Fourteen studies met the inclusion criteria. Ten studies described the extent and nature of digital health fragmentation in the United Kingdom. Digital health fragmentation affects a large number of patients and is linked to clinical care efficiency, quality, and safety risks, including limited access to external clinical records, missing or incomplete information, duplicate investigations, delays in decision‑making, and substantial time spent searching for data. Evidence specific to antimicrobial prescribing was limited (4 studies) but indicated that AMS relies on information spread across multiple systems, with poor interoperability disrupting workflows, hindering communication, and undermining stewardship activities. Only 1 study reported the development of a digital tool designed to address digital health fragmentation and support AMS. CONCLUSIONS: Digital health fragmentation negatively affects patient care across the United Kingdom, yet evidence on how it impacts AMS remains scarce. Given the urgency of the global antimicrobial resistance crisis, future research should therefore quantify the scale and impact of digital health fragmentation for AMS to inform investment and innovation in digital infrastructure and clinical-supportive solutions. TRIAL REGISTRATION: PROSPERO CRD420251126067; https://www.crd.york.ac.uk/PROSPERO/view/CRD420251126067.
PubMed2026
Incretin Mimetics for Patients Living with Type 2 Diabetes in a Predominantly Hispanic/Latino Population: Analysis of Prescribing Frequency and Predictors of Use.
PURPOSE: Studies indicate incretin mimetic utilization is relatively low, especially among patients of Hispanic/Latino ethnicity. The objective of this study was to evaluate the frequency of incretin mimetic prescribing and identify predictors of prescribing within a predominantly Hispanic/Latino population at a county-funded hospital system. METHODS: A retrospective chart review of patients living with type 2 diabetes was conducted. The primary endpoint evaluated percentage of patients prescribed an incretin mimetic during August 2023 to August 2024. The secondary endpoint evaluated predictors to prescribing such as prescriber specialty, visit(s) with an ambulatory care clinical pharmacist, insurance status, clinical laboratory values, comorbidities, and medications used for concomitant comorbidities. RESULTS: A total of 502 patients were randomly selected for review, of which 42.6% (n = 214) were prescribed an incretin mimetic. Key predictors of prescribing were: sex (OR = 0.62, 95% CI [0.41, 0.92], P = 0.019), obesity (OR = 2.65, 95% CI [1.84, 3.82], P < 0.001), hyperlipidemia (OR = 1.57, 95% CI [1.04, 2.38], P = 0.032), endocrinology clinic visit(s), (OR = 3.91, 95% CI [2.43, 6.27], P < 0.001), and visit(s) with an ambulatory care clinical pharmacist (OR = 1.72, 95% CI [1.06, 2.81], P = 0.030). There was no significant difference in prescribing for Hispanic/Latino vs non-Hispanic/Latino populations within this study. CONCLUSION: Incretin mimetics are historically underutilized among patients of Hispanic/Latino ethnicity despite their evidence-based benefits in patients with type 2 diabetes. Engagement with endocrinology and ambulatory care clinical pharmacy services may contribute to increased prescribing within clinical settings.
PubMed2026
Machine learning-driven pharmacovigilance of antidiabetic drugs: comparative reporting patterns and classification of serious adverse events.
PURPOSE: This study aims to evaluate the comparative adverse drug event (ADE) reporting patterns associated with antidiabetic drugs and develop machine learning (ML)-based classification models for the seriousness of reported ADEs. METHODS: We performed a retrospective analysis of 28,633 antidiabetic-related ADEs reported to the Korea Institute of Drug Safety and Management- Korea Adverse Event Reporting System database (KAERS DB 2505A0010) from 2015 to 2024. Disproportionality analyses identified safety signals using reporting odds ratios (RORs) with 95% confidence intervals (CIs). Factors associated with serious adverse event (SAE) classification were assessed using multivariate logistic regression, and three ML-based classification models were developed. RESULTS: Older adults accounted for 64.1% of the reported ADEs, with 2.35% classified as SAEs. Sulfonylureas demonstrated the highest SAE reporting signal (ROR 2.60, 95% CI 2.22-3.05). Male sex, older age, and sulfonylurea exposure were associated with higher odds of reports being classified as serious. Across the ML models, diabetic neuropathy treatment consistently emerged as the most influential feature contributing to SAE classification. CONCLUSION: ML-based classification complemented disproportionality analyses by identifying features associated with classification of reported ADEs as serious. Further validation using integrated longitudinal real-world data is warranted to confirm the robustness of these findings.
PubMed2026
Paediatric-Pharmacy Shared Care Improves Access and Efficiency in Developmental Paediatrics.
BACKGROUND: Rising prevalence of neurodevelopmental disorders, including attention-deficit/hyperactivity disorder (ADHD) and autism spectrum disorder (ASD), has increased demand for developmental paediatric services. Ongoing medication review requirements place increasing pressure on paediatrician-led models. Pharmacist-led shared care may improve capacity and access; however, evidence in paediatric outpatient settings remains limited. AIM: To evaluate the impact of a paediatric-pharmacy shared-care model on wait times, service capacity and efficiency compared with medical-only care. METHODS: We conducted a two-phase observational study. Phase 1 retrospectively analysed service activity from 2019 to 2024, including patient numbers, occasions of service, wait times, failure-to-attend rates, and financial outcomes. Phase 2 prospectively audited 100 pharmacist-led consultations to characterise clinical activities. RESULTS: Patient numbers increased by 87%, and the proportion receiving pharmacist-led shared care rose from 4.1% to 25.3%. Pharmacy clinics had shorter wait times than medical clinics (1.84 vs. 7.64 months; p < 0.001). Following transition to shared care, median medical occasions decreased from 3 to 2 while total occasions increased from 3 to 5 (both p < 0.001). Pharmacy clinics demonstrated greater revenue efficiency (revenue-to-cost ratio 2.97 vs. 1.73). Pharmacists conducted comprehensive medication reviews including medication counselling, adherence assessment, and non-pharmacological support within a supervised framework. CONCLUSION: The paediatric-pharmacy shared-care model was associated with shorter wait times, greater cost-efficiency, and redistribution of routine medication reviews to pharmacists, with increased overall review frequency despite fewer medical appointments per patient. Pharmacist reviews were comprehensive and delivered within a supervised framework. These findings support pharmacist-led shared care as a scalable strategy to improve access and workforce capacity in developmental paediatrics.