Context: Breast cancer is a lethal multifactorial illness among women. Recent studies have highlighted the importance of the neural network in breast tumor progression. Objectives: This review aimed to consider the potential contributions of neurotransmitters to breast cancer growth, migration, angiogenesis, and metastasis, as well as to discuss the function of neurotransmitter inhibitors in preventing tumor growth. Results: Neurons infiltrate the tumor microenvironment by secreting neurotransmitters and actively stimulate tumor progression. In breast cancer cells, neurotransmitters induce migration, growth, angiogenesis, and metastasis by regulating intracellular signaling pathways downstream of neurotransmitter receptors. Neurotransmitter inhibitors may therefore represent an alternative approach for breast cancer management. Conclusions: Neurotransmitter inhibitors might be crucial for targeting breast cancer treatment.
Background and Objective: Despite the urgent demand for the discovery of novel anticancer agents, anticancer discovery and development remain limited. Azo-containing compounds have emerged as attractive candidates in the field of anticancer drug discovery due to their distinctive reductive metabolism, which may be exploited to enhance anticancer efficacy and selectivity. Accordingly, increasing attention has been directed toward exploring the therapeutic potential of azo-aromatic scaffolds. Methods: In the present study, condensation reactions between benzoyl acetone and various aromatic diazonium salts were carried out to afford four azo derivatives, namely E-2-4-bromophenyldiazenyl-1-phenylbutane-1,3-dione KAioi, E-1-phenyl-2-phenyldiazenylbutane-1,3-dione KA102, E-2-4-methoxyphenyldiazenyl-1-phenylbutane-1,3-dione KA103, and E-2-4-nitrophenyldiazenyl-1-phenylbutane-1,3-dione KA104. Subsequent cyclization of these azo precursors provided the corresponding phenyl pyrazole derivatives, designated KA5, KA6, KA7, and KA8, respectively Results: Previously, KA5 exhibited promising anticancer activity against the human hepatocellular carcinoma cell line HepG2. The biological evaluation demonstrated that the newly synthesized KA7 is more potent than KA5, indicating that compounds exhibiting a higher propensity to exist in the hydrazone tautomeric form, particularly KA5 and KA7, showed enhanced cytotoxic activity against HepG2 cells compared with other analogues. Conclusions: These findings demonstrate that both pyrazole ring formation and tautomeric preference significantly influence anticancer activity, supporting azo-pyrazole scaffolds as promising leads for further optimization in anticancer drug development.
Background: Getting genetic material safely and efficiently into the nucleus of a cell is a monumental hurdle in gene therapy. While viruses are efficient carriers, their potential risks have pushed us to engineer smarter, non-viral alternatives. Our inspiration came from cell-penetrating peptides (CPPs), but we know that a single-function peptide is not enough; it needs to be a multi-tool capable of navigating every step of the complex delivery. Objectives: This study aimed to rationally design and optimize a modular CPP that integrates distinct functional domains to coordinate all critical stages of gene delivery: DNA binding, cellular uptake, endosomal escape, and nuclear import. Methods: In the present study, we designed a library of 30 chimeric peptides by combining functional motifs including an Hi histone-derived DNA-binding domain, the TAT membrane-translocating sequence, endosomal escape motifs such as gp4iFP and H5WYG, and the SV4o nuclear localization signal (NLS) connected by flexible linkers. Candidates were screened computationally for key properties. The lead peptide was expressed in Escherichia coli, purified, and evaluated for DNA-binding activity via gel retardation assays. Results: Computational screening identified seven top-ranked candidates, among which Peptide_24 exhibited favorable predicted stability, solubility, and pH-responsive charge characteristics. Successful recombinant expression and DNA-binding ability of Peptide_24 were confirmed experimentally for further investigations. Conclusions: This study demonstrates a rational, modular integration rather than de novo motif discovery to create a unified, multi-domain CPP architecture. Our lead candidate, Peptide_24, embodies this synergistic design, mimicking a coordinated, viral-like delivery pathway. Although computational analyses and preliminary experimental results support the potential of Peptide_24, further biological evaluation is required to assess its delivery performance in cellular systems.
Background: Nanoparticle size is a critical factor influencing diffusion behavior, interfacial interactions, and overall performance in biomedical and textile-based delivery systems. Aquilaria malaccensis (agarwood) oil (AO), an essential oil of cultural and commercial significance in Malaysia, has unique bioactive properties but remains underexplored in nanoparticle formulations due to challenges related to its volatility and poor water compatibility. Objectives: This study aims to develop a sustainable, size-tunable chitosan-based nanocarrier capable of efficiently encapsulating AO and to evaluate its physicochemical characteristics and compatibility with textile substrates for potential biomedical and functional textile applications. Methods: AO-loaded chitosan nanoparticles were produced using an emulsion-assisted ionic-gelation method, employing chitosan and sodium tripolyphosphate (TPP) without organic solvents. Particle size was modulated across a predefined design space. The optimised nanoparticle formulation was characterised for size, Polydispersity Index (PDI), zeta potential, encapsulation efficiency, loading capacity, and process yield. The optimised nanoparticles were subsequently applied onto cotton and polyester fabrics to assess wet pickup and incorporation behaviour. Results: The fabrication method produced nanoparticles ranging from 78.6 to 2425 nm with PDI values below 0.35. The optimised formulation yielded uniform particles of approximately 90.75 nm with a zeta potential of +17.6 my, an encapsulation efficiency of 80.23%, a loading capacity of 24.84%, and a process yield of 15.49%. These properties indicate effective incorporation of hydrophobic AO within the chitosan-TPP matrix. When applied to textile substrates, the nanoparticles demonstrated favourable wet pickup and incorporation profiles on both cotton and polyester. Conclusions: Overall, this work presents a sustainable and size-tunable chitosan-based nanocarrier capable of incorporating AO, highlighting its promise for future development in dermal, pharmaceutical, and biofunctional textile applications. Future research will focus on evaluating biological activity, release behavior, and textile performance, thereby establishing the practical impact and broad applicability of these nanoparticles across diverse real-world scenarios.
Background: The design of robust self-micro-emulsifying lipid formulations to enhance the bioavailability of poorly watersoluble drugs requires studying the interaction between the type of oil, co-surfactant, and type of surfactant. These blended constituents control the hydrophilicity of the lipid vehicle, drug solubility in the lipid matrix, and the physicochemical state of the drug after dispersion. Objectives: Archetypical lipid class systems were formulated, and the resultant aqueous dispersions were characterized. Ternary miscibility diagrams and physicochemical properties of the resultant dispersions with and without model drug were analyzed. Methods: Various lipid mixtures were blended by varying key elements in the vehicle composite, which include the type of oil, co-surfactant, and surfactant. Miscibility and equilibrium aqueous dispersion profiles were mapped out to screen for microemulsions. Solubility profiles of various drugs were studied in varying lipid compositions. Results: At minimal ratios of {soybean/cremophore} (1:9) or {span 80 itween 80} (2:8), only 10% w/w of tween 20 is required to obtain microemulsion dispersions. Whereas, in the case of glycerox/tween 20/cremophor RH4o, a complete region of clear emulsions was obtained at all ratios. Conclusions: Robust microemulsion lipid systems are fabricated to mimic the absorption of poorly water-soluble compounds with minimal tendency for drug recrystallization in situ after aqueous dispersion.
Background: Long-term inflammation and persistent infection can lead to chronic wounds, making them difficult to heal. Objectives: This study aimed to develop a multifunctional biopolymer-based wound dressing characterized in vitro, designed to provide an antibacterial and antioxidant microenvironment for enhanced wound healing. Methods: Accordingly, we developed a film based on chitosan-gelatin-cardamom extract to promote bacterial wound healing. Results: Scanning electron microscopy (SEM) and Fourier-transform infrared (FTIR) spectroscopy analyses showed a compact and uniform structure, with hydrogen bond formation among the functional groups of the components, indicating good compatibility. In addition, examination of the mechanical properties revealed that by applying a stress of 0.12 MPa, the maximum elongation of the hydrogel was 32.5%. Also, the swelling degree (SD) and the equilibrium water content (EWC) results illustrated that the films had optimal swelling. In the release assay, a sustained release pattern of erythromycin was observed due to the penetration of erythromycin molecules into the inner layers of the hydrogel. During the period of 7 and 8 hours, no significant difference was observed in the release of the drug, and it reached a steady-state plateau. For assaying the antibacterial function of the films, Staphylococcus aureus and Escherichia coli were incubated with the films for 24 h. The chitosan-gelatin-cardamom-erythromycin group showed enhanced inhibition of S. aureus, attributable to the synergistic effect of the drug and the extract. Antioxidant activity assays of the films using 2,2-diphenyl-1-picrylhydrazyl (DPPH) and ferric reducing antioxidant power (FRAP) methods revealed that this group had strong antioxidant capacity. Cytotoxicity analysis using the methylthiazolyldiphenyl-tetrazolium bromide (MTT) assay showed that the films maintained high biocompatibility, with cell viability exceeding 90% compared to the untreated control. Conclusions: Collectively, chitosan-gelatin-black cardamom extract film, with its antioxidant, antibacterial, and suitable biocompatibility properties, may serve as a potential wound dressing for bacterial-infected wounds.
Background: Intrauterine insemination (IUI) is among the most common methods for individuals with infertility. Objectives: This study aims to assess the pregnancy rates (laboratory and clinically) following simultaneous IUI with human chorionic gonadotropin (hCG) triggering and those performed 36-40 hours following the hCG triggering. Methods: In this open-label randomized controlled trial, a total of 248 couples were randomly (1:1 ratio) assigned to either the intervention (challenging method) or control (conventional method) group. Laboratory- and clinically-confirmed pregnancy were considered the main outcome. This study used intention-to-treat analysis, and any P-value less than 0.05 was considered statistically significant. Results: Total numbers of laboratory- and clinically-confirmed pregnancies, which were the same in each arm (N = 124), were significantly higher (P-value = 0.038) in the intervention group (N = 31; 25.00%) compared to the controls (N = 18; 14.52%). Moreover, to address the effect of covariates, especially those with chance imbalance (sperm count and morphology), multivariable logistic regression models were performed with and without the allocated treatment group. Following this, the models revealed that no covariate, except the allocated treatment, had a statistically significant effect (OR = 2.22, 95% CI: 1.09 to 4.53) on the outcome. Conclusions: According to the results, it seems that simultaneous hCG triggering with IUI could improve the pregnancy rate; however, further pragmatic trials are required.
Context: Endocrine therapy remains the standard of care for hormone receptor-positive (HR+) and human epidermal growth factor receptor 2-negative (HER2-) advanced breast cancer (BC), but its efficacy is limited in patients with prior endocrine exposure. Cyclin-dependent kinase 4/6 inhibitors (CDK4/6i), such as palbociclib, have emerged as a promising strategy to enhance treatment outcomes. Objectives: This systematic review and meta-analysis aimed to evaluate the efficacy of palbociclib combined with endocrine therapy (ET) versus endocrine therapy alone in improving survival outcomes. Methods: A systematic literature search was conducted in PubMed, Scopus, and Web of Science up to November 9, 2025, following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Randomized controlled trials (RCTs) comparing palbociclib plus ET with ET alone or placebo plus ET in HR+/HER2– advanced or metastatic BC patients were included. Outcomes assessed were progression-free survival (PFS) and overall survival (OS). Hazard ratios (HRs) and 95% confidence intervals (CIs) were pooled. Results: Seven RCTs, including 1,758 patients, met inclusion criteria. Pooled analysis demonstrated that palbociclib combined with ET significantly improved PFS compared with ET alone (HR = 0.492; P < 0.001). A trend toward improved OS was observed (HR = 0.883; P = 0.075), though this did not reach statistical significance. Subgroup analyses and bias assessments confirmed consistent efficacy across populations and low risk of methodological bias, with no evidence of publication bias. Conclusions: Palbociclib combined with ET provides substantial improvements in PFS and demonstrates a favorable trend in OS for patients with HR+/HER2– advanced BC.
Background: The essential oil of Dracocephalum lindbergii (Lamiaceae) contains bioactive compounds with potential therapeutic properties. Objectives: The present study evaluated the genotoxic effects of D. lindbergii essential oil. Methods: Essential oil was extracted from the plant using the Clevenger method and analyzed by gas chromatography-mass spectrometry (GC-MS) to determine its chemical constituents. Genotoxicity was evaluated in human umbilical vein endothelial cells (HLIVECs) using the comet assay by gel electrophoresis with fluorescent dyes. Intracellular antioxidant activity was assessed by measuring glutathione (GSH) levels and reactive oxygen species (ROS) generation. Absorption, distribution, metabolism, excretion, and toxicity (ADMET) properties of the main compounds in the essential oil were evaluated using an in silico approach. Results: The GC-MS analysis identified limonen40-yl-acetate as the predominant compound in the essential oil, accounting for 66362% of the total ion chromatogram (TIC). Unidentified compounds constituted 8.084% and 12350% TIC, indicating additional biologically active molecules. Minor constituents included monoterpenes such as limonene and d-3-carene (3.104% and 4.294% TIC, respectively), and the sesquiterpene germacrene (3.131% TIC), suggesting a chemically diverse extract. The comet assay demonstrated that the essential oil did not induce DNA damage at low concentrations but exhibited genotoxic effects at doses exceeding 10 og/mL. Furthermore, treatment with the essential oil led to increased intracellular ROS levels and reduced GSH, suggesting a potential oxidative stress-mediated mechanism underlying the observed DNA damage. Based on admetSAR predictions, limonene 10 yl acetate displayed drug-like behavior. Conclusions: The phytochemical profile of D. lindbergii essential oil indicates a predominance of monoterpenoid compounds, with limonen40-yl-acetate as the main component. While the MTT assay indicated weak toxicity on HUVEC cells with an ICso of 7073 pgimL, experimental data demonstrate that the oil induces concentration-dependent DNA damage, reduces intracellular antioxidants, and elevates ROS levels in HUVEC cells, indicating its genotoxic and oxidative potential in vitro at higher doses. These effects raise preliminary concerns about its safety, highlighting the need for additional research into in vivo toxicity, mechanisms of action, and the role of unidentified compounds to ensure responsible use in human medical and cosmetic applications.
Background: Human immunodeficiency virus type 1 (HIV-1) protease is essential for viral maturation and remains one of the most important therapeutic targets in antiretroviral therapy. Darunavir (DRV), a potent second-generation protease inhibitor, serves as a reference compound due to its high binding affinity and broad activity against resistant viral strains. However, drug resistance among newer strains continues to challenge therapeutic optimization. Objectives: In this study, four DRV-like inhibitors with different stereochemical configurations and substituents were investigated to elucidate the dynamic determinants of inhibitory potency. Methods: Molecular docking established the binding orientations of the inhibitors within the protease active site, while 200 ns all-atom molecular dynamics (MD) simulations provided detailed insights into conformational stability, flap flexibility, and secondary structure remodeling. Results: Analyses of root mean square deviation (RMSD), root mean square fluctuation (RMSF), solvent-accessible surface area (SASA), define secondary structure of proteins (DSSP), principal component analysis (PCA), and radius of gyration (Rg) revealed that high-potency inhibitors induce more pronounced conformational rearrangements, increased flap mobility, and adaptive secondary structure transitions. These dynamic features correlate strongly with experimentally obtained inhibitory constant (Ki) values. Conclusions: Overall, the findings deliver atomistic and mechanistic insights into inhibitor recognition and potency, offering predictive guidance for the rational design of next-generation HIV-1 protease inhibitors with enhanced efficacy and resistance resilience.
Background: The interaction between epidermal growth factor (EGF) and its receptor (EGFR) is a critical process in wound healing, owing to their role in initiating epidermal and dermal regeneration. EGF-based therapies enhance wound healing, and engineered EGF mutants with increased EGFR binding are designed to further improve this effect. Objectives: This study aimed to utilize molecular dynamics simulations (MDS) to comprehensively analyze the interactions between EGF mutants and EGFR, providing mechanistic insights that could inform the design of novel therapeutics for wound healing and regenerative medicine. Methods: Molecular dynamics simulations were performed to investigate the key molecular interactions and binding dynamics between wild-type EGF (WT-EGF) and two engineered EGF mutants (m28-EGF and m123-EGF) in complex with EGFR. Comparative analyses of structural stability, binding affinity, and interaction energy were conducted to elucidate the molecular basis of enhanced receptor activation by these mutants. Results: Molecular dynamics simulation results indicated that the introduced mutations rendered the EGF mutants less flexible, allowing them to adopt more compact and stable structures. Accordingly, the mutations in m28-EGF and m123-EGF significantly affected their binding affinity to EGFR, with m28-EGF exhibiting a preference for domain I and m123-EGF showing a preference for domain III of EGFR. Additionally, analysis of the EGFR dimerization domain revealed that the EGFR chains in the mutant complexes demonstrated an increased capacity to form hydrogen bonds and hydrophobic interactions compared to the wild type. Notably, the calculated interaction energies in the m123-EGF/EGFR complex were higher than those in other complexes, indicating a stronger binding affinity. These findings underscore the pivotal contribution of domain II to EGFR dimer stability and its essential role in maintaining the EGF-EGFR interaction. Conclusions: These results suggest that EGF super-agonists hold significant promise in regenerative medicine and that targeting ligand-receptor interactions can facilitate therapeutic development to modulate EGFR signaling. Understanding how ligands induce conformational changes in EGFR could lead to new treatments and personalized medicine for EGFR-related diseases, although the diverse effects of different ligands warrant further investigation.
Background: Drug allergies are a significant cause of skin rashes in children, influencing treatment approaches and outcomes. However, data on causative agents and clinical patterns in the Middle East, particularly Iran, are limited. Objectives: This hospital-based cross-sectional study evaluated drug history and patterns of allergic reactions in children with suspected cutaneous adverse drug reactions (CADRs) at a hospital in Zahedan, Iran. Methods: In this cross-sectional study, 210 pediatric patients with suspected CADRs were enrolled between January 1 and December 31, 2023. Data on demographics, drug history, clinical manifestations, and family allergy history were collected using a structured questionnaire and medical record review. The Naranjo algorithm was applied for causality assessment. Data were analyzed using IBM SPSS Statistics for Windows, Version 26.0. Descriptive statistics and chi-square tests were used; a P-value < 0.05 was considered significant. Results: The mean age was 7.1 ± 4.3 years, with 51% males and 49% females. A history of drug exposure preceding rash onset was reported in 82.2% of cases. Antibiotics (32.2%) and anticonvulsants (27.8%) were the most common triggers, followed by nonsteroidal anti-inflammatory drugs (NSAIDs, 10%) and herbal medicines (12.2%). Urticaria/angioedema (45.5%) and maculopapular rash (30%) were the predominant clinical presentations. A family history of drug allergy was present in 43% of cases. Urticaria/angioedema was significantly more common in boys (P = 0.01), while maculopapular rash and anticonvulsant reactions were more frequent in girls (P = 0.03 and P < 0.001, respectively). Conclusions: Antibiotics and anticonvulsants are the principal causes of CADRs in children, with urticaria/angioedema being the most prevalent presentation. The high prevalence of herbal medicine reactions and family history of drug allergy underscores the need for meticulous evaluation and cautious prescribing. These findings highlight the importance of enhanced pediatric pharmacovigilance systems to improve drug safety.
Background: Calcineurin inhibitors (CNIs), such as tacrolimus (TAC), remain central in transplantation and autoimmune disease management; however, adverse effects, particularly hyperglycemia, frequently complicate their use. Kaempferol (KF), a flavonol with hypoglycemic and antioxidant properties, has been proposed as a potential adjunctive modulator of CNI-related toxicities. Objectives: This study investigated the mechanisms of TAC-induced hyperglycemia, focusing on oxidative stress and calcineurin B1 (CnB1) expression, and assessed the protective effects of KF. Methods: Twenty-four male Wistar rats (180 - 230 g) were randomized into three groups (n = 8/group) and treated for 30 days: (1) The TAC 0.6 mg/kg/day intraperitoneally, (2) TAC + KF 10 mg/kg/day orally, and (3) vehicle controls. Blood samples were collected at days 15 and 30 to measure TAC trough levels, glucose, and insulin by enzyme-linked immunosorbent assay (ELISA). Pancreatic tissues were analyzed for oxidative stress markers [malondialdehyde (MDA), superoxide dismutase (SOD), and glutathione (GSH)], P-glycoprotein (P-gp), and CnB1 expression. Molecular docking (MD) was also performed to assess KF interactions with calcineurin subunits. Results: The TAC monotherapy markedly increased serum glucose (128% at day 15; 150% at day 30 vs. controls, P < 0.005) and reduced insulin levels (-81% at day 15; -85% at day 30, P < 0.005). The TAC also elevated pancreatic MDA (+1113%) while significantly suppressing CnB1 expression (-98.4%). Co-administration of KF significantly reduced TAC trough levels by 29% at day 30 (P < 0.005), attenuated hyperglycemia (glucose reduction by 35% at day 15 and 50% at day 30 vs. TAC, P < 0.005), and restored insulin levels (+143% and +350% at days 15 and 30 vs. TAC, P < 0.005). In the pancreas, KF lowered MDA (-62%, P < 0.001), enhanced antioxidant defenses (GSH +128%, SOD +68%), and reversed TAC-induced CnB1 suppression (+408%, P < 0.01). The MD supported a moderate binding of KF to both calcineurin A (CnA) and CnB1 chains, providing a mechanistic basis for its effects. Conclusions: The MD analysis revealed that several flavonoids exhibit promising binding affinities toward CnB1, CnA, and cyclophilin. These findings suggest that flavonoids may possess potential immunomodulatory properties through modulation of the calcineurin pathway. Therefore, further comprehensive investigations — combining advanced MD, molecular dynamics simulations, and in vitro as well as in vivo experimental validation — are essential to confirm the mechanistic roles, efficacy, and safety of flavonoids as potential immunomodulatory agents.
Background: Particle size strongly affects antibiotic efficacy by influencing drug permeability and tissue penetration. Vancomycin (VCM) hydrochloride, due to its large hydrophilic nature, cannot effectively cross the intestinal barrier and is usually given intravenously. Reducing particle size to nanoparticles is a strategy to improve absorption and transport across biological membranes. Objectives: The present study evaluated the intestinal permeability coefficient and the orally absorbable fraction of VCM nanoparticles in comparison to their conventional form. Methods: The single-pass intestinal perfusion (SPIP) technique was used to evaluate the effective permeability (Peff), fraction absorbed (Fa), and total absorption of VCM in nanoparticle and solution forms at concentrations of 200, 300, and 400 µg/mL, with a flow rate of 0.2 mL/min for 80 minutes. Results: The data revealed that the Peff of VCM in nanoparticle form was 2.16, 1.43, and 2.66 times greater than that of conventional VCM at concentrations of 200, 300, and 400 µg/mL, respectively. Stability testing further showed that VCM nanoparticles remained intact with no signs of degradation after 0, 1, and 2 hours. Conclusions: These results indicate that VCM nanoparticles have the potential to enhance intestinal permeability and may represent a promising approach for oral delivery, pending confirmation in further in vivo and clinical investigations.
Background:Prangos platychlaena Boiss. and Cachrys scabra (Fenzl) Meikle are two distinct genera from the Apiaceae family that grow naturally in the Halgurd Mountains of Iraqi Kurdistan. These genera are traditionally used in medicine and as food flavoring agents across the world, particularly in the Middle East. Objectives: This study aimed to investigate the antimicrobial and antioxidant potential of essential oils (EOs) obtained from two endemic plants of Iraqi Kurdistan, P. platychlaena and C. scabra. Methods: The antioxidant and antibacterial activities of EOs extracted by steam distillation from the leaves and flowers of P. platychlaena and C. scabra collected from the Halgurd Mountains were evaluated. Results: Overall, the EOs exhibited stronger inhibitory effects against ABTS radicals than against DPPH radicals. Cachrys scabra flower essential oil (CSFEO) and leaf essential oil (CSLEO) showed the weakest radical scavenging activity, with IC50 values of 2534 +/- 0.73 mg/mL and 25.09 +/- 1.31 mg/mL, respectively. Furthermore, the EOs from both plants demonstrated good antibacterial efficacy against all tested microorganisms, except Pseudomonas aeruginosa (ATCC 27852), which was not affected by any of the EOs. The growth inhibition zones (GIZ) of sensitive strains ranged from 10 +/- 0.5 mm to 20 +/- 1.8 mm. Conclusions: The EOs of P. platychlaena and C. scabra possess antioxidant activity capable of scavenging DPPH and ABTS radicals and exhibit antibacterial effects against both gram-positive and gram-negative bacteria. These findings suggest that these EOs may serve as promising natural preservatives for use in the pharmaceutical and food industries.
Introduction: Drug reaction with eosinophilia and systemic symptoms (DRESS) is a rare but potentially fatal hypersensitivity reaction associated with a range of medications, including aromatic anticonvulsants such as lamotrigine. This syndrome is characterized by delayed onset, fever, rash, hematologic abnormalities, and multi-organ involvement. Although eosinophilia is often considered a hallmark, its absence does not rule out the diagnosis. Case Presentation: We present the case of a 40-year-old man with intellectual disability and chronic polypharmacy who developed DRESS syndrome three weeks after the initiation of lamotrigine. His clinical course was marked by fever, diffuse skin rash, hepatic dysfunction, and acute anuric renal failure requiring dialysis. Laboratory evaluation revealed markedly elevated liver enzymes, high inflammatory markers, and atypical lymphocytosis without eosinophilia. Despite initial improvement following high-dose intravenous corticosteroids, the patient experienced sudden pancytopenia, respiratory failure, and ultimately died from suspected sepsis. Conclusions: A comprehensive review of 34 reported cases of lamotrigine-induced DRESS showed significant heterogeneity in clinical presentation, with 18% lacking eosinophilia and only limited viral reactivation testing reported. Notably, severe renal involvement such as seen in this case was rare, emphasizing the spectrum of disease severity. This report highlights the diagnostic challenges of DRESS syndrome, particularly in atypical presentations and vulnerable populations. It underscores the importance of early recognition, comprehensive diagnostic workup - including consideration of viral reactivation - and prompt withdrawal of the offending agent. Clinician awareness of atypical features, such as the absence of eosinophilia and fulminant organ failure, is critical for timely diagnosis and intervention.
Background: The atomic interactions between hormone receptors and drugs are a fascinating area of study that holds great promise for the development of novel gastrointestinal therapeutic interventions. By understanding the structural basis of these interactions, researchers can design drugs with improved efficacy and reduced side effects. Objectives: In the current research, we used molecular dynamics simulations (MDS) to predict atomic interactions between the t-anethole drug and target hormone receptors (6KS0 adiponectin, 6HSE ghrelin, 8DHA leptin, and 7X9C neuropeptide Y). Methods: For this purpose, designed atomic structures were equilibrated at STP conditions under NVT/NVE ensembles. The equilibrium phase of samples was detected by the convergence of kinetic and total energies over simulation time (10 ns -100 ns). After detecting the equilibrium phase, the atomic interaction between the drug and target receptors was introduced by implementing a micro-canonical ensemble. Numerically, the binding energy between the drug and hormone receptors converged to 0.24, 0.17, 0.22, and 0.19 kcal/mol, respectively. The binding energies represent the strength of the interaction between a drug and its receptor, affecting drug binding affinity, duration of action, and efficacy. Results: Simulation numerical results predicted that the t-anethole drug and adiponectin receptors attracted with more intensity, and this procedure caused the drug delivery to occur with more intensity. Conclusions: This study underscores the promise of trans-anethole (TA) as a natural therapeutic compound for enhancing metabolic health by influencing adiponectin signaling pathways. Additional experimental validation is essential to substantiate these computational predictions and to assess the clinical implications of TA in the context of metabolic disorders, particularly concerning insulin resistance and obesity.
Background: Nitisinone is a potent inhibitor of 4-hydroxyphenylpyruvate dioxygenase, the second enzyme involved in the tyrosine catabolic pathway. It is used for treating hereditary tyrosinemia type 1. Enzyme deficiency results in the accumulation of metabolites such as maleylacetoacetate and fumarylacetoacetate. The accumulation of these harmful metabolites can damage the liver and kidneys. Inhibiting 4-hydroxyphenylpyruvate dioxygenase with nitisinone reduces these metabolites. Objectives: Until now, simple and convenient spectrofluorimetric and spectrophotometric methods for determining nitisinone in capsules as a pharmaceutical product have not been developed and validated. These methods facilitate affordable quality control in environments with limited resources. Methods: To achieve simpler and more accessible methods to determine the amount of nitisinone in its pharmaceutical dosage forms, this study utilized a spectrofluorimetric method based on the fluorescence quenching of fluorescein following the charge transfer complex formation of nitisinone with fluorescein at pH 6. Furthermore, zero, second, and third-order derivative spectrophotometric methods were also used for nitisinone determination. Results: Beer's law was obeyed for the spectrofluorimetric and spectrophotometric methods (concentration ranges of 0.1 - 3 pg/mL and 0.1- 5 pg/mL, respectively). Conclusions: The developed methods were employed to assess nitisinone in capsule form as a pharmaceutical dosage form and were compared with a high-performance liquid chromatography (HPLC) method. Statistical analysis indicated no significant difference between the results obtained from these methods.
Background: The expanded utility of herbal medicines worldwide has created a demand to determine the possible adverse effects of these plants to protect people from exposure to them. Objectives: The present study evaluated the acute and sub-chronic toxic effects of Achillea wilhelmsii extract on Wistar male and female rats to provide an accurate median lethal dose (LD50) and suggest a value for the no observed adverse effect level Methods: In both phases, Wistar rats were assigned to control and intervention groups. At the end of the study, blood was collected from the heart for hematological analysis and from the retro-orbital sinus for serum biochemical assessment. Then, the heart, kidney, liver, lung, and spleen tissues were collected for histopathological studies. Results: In the acute phase of the study, no mortality was reported. Additionally, there were no significant changes in the body and organ weights in rats from all groups after 14 days at the dose of 5000 mg/kg. In the sub-chronic phase, after 60 days of oral consumption of 250, 500, and1000 mg/kg of the extract, there were no significant body and organ weight changes between the control and treatment groups (P > 0.05). Hematological and biochemical analyses revealed no changes in the organs' functional activity. Conclusions: Acute and repeated oral consumption of herbal medicines containing A. wilhelmsii extracts appears to be nontoxic up to the tested doses (LD50 > 5000 mg/kg, NOAEL >1000 mg/kg).
