Search Results (2,021)

Current treatment options for hair loss remain limited. Therefore, this study compared a botanical extract derived from multiple plants with the pharmaceutical agent minoxidil for topical application. The evaluated parameters included inflammatory cytokines (IL-1β, IL-6, TNF-α), growth factors (TGF-β, VEGF, KGF), and 5α-reductase type II (SRD5A2) expression in the human keratinocyte cell line HaCaT, as measured by ELISA. Both the botanical extract and minoxidil reduced IL-6 levels by 21% and 35%, and TNF-α levels by 13% and 35%, respectively. Treatment with the botanical extract and minoxidil increased VEGF expression by 50% and 85%, and KGF by 16% and 31%, respectively, while reducing SRD5A2 expression by 21% and 28%, respectively. Overall, the results of this in vitro study suggest that the botanical extract exhibits a response pattern similar to that of minoxidil, characterized by the suppression of pro-inflammatory cytokines and SRD5A2, along with enhanced expression of growth factors VEGF and KGF in HaCaT cells. These results provide a promising basis for further in vivo studies. Full article

Perillyl alcohol, a rare monoterpenoid, can be widely used in chemical, agriculture, and food industries and shows promise in medicine as an anticancer agent. The artificial synthesis of perillyl alcohol from β-pinene epoxide using inexpensive and abundant turpentine is chosen for improving its pharmaceutical and industrial applications. This work presents a green and sustainable catalytic process for the rearrangement of β-pinene epoxide to perillyl alcohol. A novel ammonium phosphomolybdate solid acid (AC-COIMI-NH₄PMo) was built via phosphomolybdic acid chemisorption onto an N-basylous site of imidazolized activated carbon followed by ammonia fumigation, which exhibits outstanding catalytic performance in the rearrangement of β-pinene epoxide to perillyl alcohol in nitromethane under mild conditions. At 80 °C over 80 min, nearly complete conversion of the epoxide is achieved with a perillyl alcohol selectivity of 77.3%. Moreover, the used catalyst can be readily recycled after washing with hot nitromethane. The favorable proton-donating capacity of nitromethane for the rearrangement and the comparison of adsorption energies between substrates and main products on ammonium phosphomolybdate are revealed through DFT calculation. Kinetic analysis based on the Langmuir adsorption model indicates that the surface reaction of strongly adsorbed β-pinene epoxide is a rate-determining step and follows a zero-order reaction process; the activation energy is 29.64 kJ/mol within the temperature range of 50–80 °C. Finally, a parallel catalytic rearrangement mechanism is proposed, and an eight-step reaction pathway toward perillyl alcohol is elaborated for β-pinene epoxide conversion on AC-COIMI-NH₄PMo. Full article

At present, treated wastewater may still contain residual nutrients and micropollutants, including heavy metals, pharmaceuticals, and dyes, which can negatively affect receiving water bodies. Increasingly stringent environmental regulations, including Directive (EU) 2024/3019, require both enhanced removal of these contaminants and greater integration of renewable energy sources in wastewater treatment plants. This paper presents a review of biomass-based wastewater polishing technologies employing biological agents such as microalgae, fungi, bacteria, co-cultures and duckweed for the removal of residual contaminants from treated effluents. The compiled data indicate that while optimal conditions can drive pollutant removal efficiencies beyond 90%, system performance varies widely depending on species selection, wastewater characteristics, and operational conditions (e.g., pH, temperature, salinity, nutrient availability, and light intensity). In addition to effluent polishing, the produced biomass can be valorized for bioenergy generation, contributing to renewable energy production and supporting circular economy principles in wastewater treatment plants. Despite these benefits, biomass harvesting remains a major technical and economic bottleneck, often representing a significant share of operational costs and limiting large-scale implementation. Overall, biomass-based treatment technologies are a promising approach for improving effluent quality and supporting renewable energy objectives; however, further advances in biomass recovery are required for broader application. Full article

Aquatic ecosystems are under severe stress from a diverse combination of contaminants, including heavy metals, pesticides, pharmaceuticals, and microplastics, driven by rapid industrialization, intensive agriculture, and urbanization. Globally, 80% of wastewater remains untreated, and conventional systems often fail to address emerging contaminants. Consequently, toxic heavy metals like lead and mercury can persist in water sources for decades. In response, phytoremediation has emerged as a scalable, eco-friendly, nature-based alternative. Among phytoremediation agents, duckweeds are increasingly recognized for their rapid growth, simple morphology, and continuous water-column contact. This review outlines the landscape of duckweed-based remediation, detailing molecular detoxification pathways and the synergistic role of associated microbiomes in enhancing environmental cleanup. Evidence indicates that contaminant removal is often supported by plant-microbe interactions. Despite extensive laboratory validation, field-scale implementation remains constrained by environmental complexity, pollutant mixtures, and variable climatic conditions. Furthermore, while duckweed systems hold promise within circular bioeconomy frameworks, converting wastewater into nutrient-rich biomass, contaminant accumulation in plant tissues raises concerns about biomass utilization and contaminant carryover. Addressing these challenges requires an integrative approach that links molecular detoxification, ecological interactions, and engineered system design to realize the full potential of duckweeds for sustainable aquatic pollution management. Full article

Introduction: Fish and humans share evolutionarily conserved pathways regulating lipid metabolism. However, the effects of pharmaceuticals on lipid homeostasis in fish remain poorly understood, particularly regarding mechanistic lipid dysregulation and its implications for fish physiology and environmental toxicology. While hypolipidemic drugs such as statins have been shown to modulate lipid metabolism in teleosts, other lipid-lowering agents, including cholesterol absorption inhibitors, remain largely unexplored. Additionally, synthetic hormones have been shown to interfere with lipid regulation, although their effects—particularly those of progestins—remain poorly characterized. Objective: This study aimed to explore the mechanistic lipid disruptions induced by potential hypo- and hyperlipidemic modulating pharmaceuticals in brown trout juveniles exposed to subchronic pharmacological conditions. Methodology: Juvenile brown trout were exposed via intramuscular injection every 72 h for 28 days and allocated into six experimental groups (n = 12 per group): control (C; 0.7% NaCl), solvent control (SC; 0.7% NaCl, 0.9% ethanol, 0.1% dimethyl sulfoxide), atorvastatin (ATV; 0.3 µg·g⁻¹), ezetimibe (EZB; 0.3 µg·g⁻¹), 17α-ethinylestradiol (EE2; 2 µg·g⁻¹), and levonorgestrel (LNG; 0.1 µg·g⁻¹). All concentrations represented pharmacological doses. On day 28, the fish were euthanized and sampled. Endpoints included biometric measurements, blood lipid profiling, serum biochemistry, and hepatic lipid accumulation. Results: ATV fish displayed greater body length, whereas EE2 increased liver weight and hepatosomatic index. EE2 reduced high-density lipoproteins and increased low-density lipoproteins, while atorvastatin reduced low-density lipoproteins. EE2 exposure also increased albumin levels and decreased glucose concentrations. Furthermore, EE2 significantly enhanced hepatic lipid deposition. Conclusions: The hyperlipidemic effects of EE2 were the most pronounced, whereas ATV produced the strongest hypolipidemic responses, consistent with its known effects in humans, and also influenced biometry. These findings provide a robust foundation for understanding how pharmaceuticals influence lipid metabolism and related physiological processes such as growth in fish, with relevance for both fish physiology research and environmental toxicology. Full article

Background: Alcohol use disorder (AUD) is a grave mental health condition that can result in significant health and social consequences. The medications Naltrexone and Nalmefene are indicated for the treatment of AUD, with Naltrexone having received the most extensive research attention. Methods: The majority of papers assessing universal measures of alcohol consumption employed two primary metrics: total alcohol consumption (TAC) and the number of days per month where individuals engaged in heavy drinking (HDD). Indicators pertaining to the maintenance of complete abstinence were excluded due to the absence of sufficient data. The safety of both substances was also assessed, as were the frequency of side effects and independent patient dropout. The study also incorporated practical factors of the therapy, such as the route of administration, dosage regimen, and the drug’s patient convenience, which can have a significant impact on adherence to therapy. Results: Nalmefene, administered in an “as needed” regimen, demonstrated statistically significant activity in reducing HDD and total alcohol consumption (TAC) among patients with AUD, particularly those with elevated World Health Organization (WHO) DRL risk. Preliminary findings from the ESENSE1 (Efficacy of Nalmefene in Alcohol Dependence; the first phase III study), ESENSE 2 (Efficacy of Nalmefene in Alcohol Dependence, the second phase III study), and SENSE (the final phase III long term-safety and cost-effectiveness study) studies indicate a substantial decrease in HDD and TAC following the initial month of treatment. These effects persist throughout the subsequent follow-up period. Several Japanese studies have corroborated the effectiveness of Nalmefene, demonstrating its efficacy across both short-term and long-term applications. Furthermore, these studies have substantiated its safety profile, indicating that there is no inherent risk of addiction or the emergence of withdrawal symptoms. The mild nature of adverse events (most commonly nausea and dizziness) led to a relatively low discontinuation rate of Nalmefene treatment. A subsequent study, employing a recognized methodology, corroborated the efficacy of psychosocial support in enhancing treatment outcomes. Meta-analyses demonstrate that Naltrexone exhibits comparable efficacy in reducing the frequency and severity of alcohol consumption. In select populations, the injectable form (LAI) of this pharmaceutical agent facilitates less frequent dosing, which is advantageous for the treatment process. A comparison of Nalmefene and Naltrexone reveals that the latter does not demonstrate a significant impact on the likelihood of individuals returning to heavy alcohol consumption. Conclusions: In the treatment of AUD, both naltrexone and nalmefene have been shown to yield positive outcomes, particularly in terms of reducing the HDD and TAC. According to the World Health Organization (WHO) classification, Nalmefene is indicated for individuals with a high risk of developing serious conditions. It has been demonstrated to produce rapid and sustained results while exhibiting a favorable safety profile, characterized by the absence of significant adverse effects. Naltrexone is a medication that has proven to be effective. LAI may have a positive impact on the efficacy of treatment. Full article

The rational design of mixed micellar systems has emerged as a cornerstone of modern nanomedicine, offering unprecedented control over the solubility and bioavailability of challenging therapeutic agents. This review provides a comprehensive analysis of the physicochemical principles governing the assembly of amphiphilic drugs and surfactants into synergistic nanostructures. By articulating the transition from traditional guest/host solubilization to “drug-as-component” models, we highlight the critical role of molecular interactions in achieving therapeutic precision. It further outlines the experimental methodologies used to investigate these systems and elucidates how they enhance the solubility, stability, and bioavailability of poorly water-soluble drugs. Special emphasis is placed on the practical applications of synergy in reducing systemic toxicity and optimizing drug release kinetics, providing a roadmap for the development of next-generation nano-pharmaceuticals. The functionality of these systems is significantly influenced by the molecular interactions among their constituents; thus, quantitative analysis of these interactions might enhance the formulation of more effective pharmaceuticals. This review outlines the key physicochemical principles of mixed micelle formation, including thermodynamics and synergistic interactions of amphiphiles, while emphasizing their relevance in current research and practical pharmaceutical applications. Various experimental methods, such as surface tension measurement, conductometric and calorimetric tests, and spectroscopic techniques, are compared in terms of their conditions of application and performance in understanding micelle formation and micelle structure. We clearly point out that the interpretation and evaluation of the properties of colloidal systems containing drug molecules solubilized by mixed micelles and an amphiphilic drug incorporated into micelles must be discussed and evaluated separately. Understanding the limitations and characteristics of the physical/chemical principles applied is essential for the rational design of mixed micelle carriers tailored to specific therapeutic needs. Full article

Background/Objectives: Cyclotides are plant-derived macrocyclic peptides distinguished by their head-to-tail cyclized backbone and cystine knot motif, which confer remarkable stability against thermal, enzymatic, and chemical degradation. These features, combined with a compact and rigid structure, position cyclotides as promising scaffolds for future antibacterial agents in response to the escalating threat of multidrug-resistant (MDR) pathogens and the stagnation of conventional antibiotic discovery pipelines. This review summarizes the structural features, antibacterial mechanisms, bioengineering strategies, and translational potential of cyclotides against MDR infections. Methods: A narrative review of the literature was conducted using recent original research articles and reviews on cyclotide structure, antibacterial activity, bioengineering, computational modeling, and pharmaceutical applications. Results: Cyclotides exhibit potent antimicrobial activity, primarily through membrane disruption mediated by amphipathic surfaces and affinity for anionic bacterial membranes. Some variants also demonstrate anti-virulence and antibiofilm properties, broadening their therapeutic relevance for difficult-to-treat infections. Bioengineering approaches, including epitope grafting and rational design, have improved selectivity and potency while reducing cytotoxicity. Advances in computational modeling, molecular dynamics, and artificial intelligence have accelerated the prediction and optimization of antimicrobial activity, toxicity, and pharmacokinetic properties. Conclusions: Innovations in synthesis, including recombinant expression and enzymatic ligation, are helping overcome translational barriers related to cost and scalability. Although challenges remain in oral bioavailability and systemic delivery, strategies such as lipidation and scaffold modification support the development of cyclotide-based therapeutics as adaptable platforms for peptide drug discovery. Full article

Efficient delivery systems are essential for transporting chemotherapeutic agents to target sites, enhancing cellular uptake and reducing off-target side effects. Peptides, owing to their intrinsic biocompatibility and structural tunability, have emerged as promising carriers for delivering labile chemotherapeutics and improving pharmacokinetics and therapeutic outcomes. Along these lines, a wide variety of peptide-based delivery strategies have been developed to achieve desirable pharmaceutical properties for anticancer agents. Particularly, stimuli-responsive peptide-based nanocarriers have attracted high levels of attention due to their ability to exploit overexpressed or tumor-specific stimuli, enabling selective disassembly and controlled drug release within cancer cells. In this review, we highlight recent advances in the development of stimuli-responsive peptide nanocarriers and their applications in anticancer therapy, and discuss key challenges and future directions toward their clinical translation. Full article

Bifurcaria bifurcata R. Ross 1958 is a perennial brown seaweed belonging to the Sargassaceae family and represents an underexploited marine bioresource with promising applications in the sustainable food and pharmaceutical sectors. To support its sustainable valorization as an alternative to synthetic additives, this study provides a comprehensive evaluation of the chemical composition, bioactivity, and mineral profile of B. bifurcata to support its valorization. The essential oil, obtained by hydrodistillation and characterized by GC—MS, revealed a rich chemical profile comprising 51 compounds, of which 42 were identified, accounting for 95.37% of the total composition. The major constituents included 2′-hydroxy-4′,5′-dimethylacetophenone (13.11%), benzene, 1-ethyl-3,5-dimethyl- (9.79%), 1,5,9-cyclododecatriene, 1,5,9-trimethyl- (8.57%), and benzene, 1-(1,1-dimethylethyl)-4-methoxy- (8.52%). The essential oil exhibited moderate antioxidant activity under in vitro conditions, with a total antioxidant activity of 74.85 ± 2.78 mg E α-tocopherol/g and IC₅₀ values of 0.103 ± 0.004 (DPPH), 0.106 ± 0.002 (FRAP), and 2.672 ± 0.123 mg/mL (β-carotene bleaching assay). In addition, notable antibacterial activity was observed against Escherichia coli, Staphylococcus aureus, Bacillus subtilis, and Listeria monocytogenes, with inhibition zones ranging from 10 to 12 mm. Mineral analysis of the seaweed powder highlighted its nutritional importance, with high levels of organic matter, proteins, and sugars, along with substantial concentrations of essential macroelements (K, Ca, Mg, and Na) and trace elements (Fe, Mn, and Zn). Overall, these findings demonstrate the potential of B. bifurcata as a sustainable marine resource for the development of natural antioxidants, antimicrobial agents, and mineral-rich ingredients, contributing to environmentally friendly food systems and green pharmaceutical applications. Full article

The Senegal tree (Sengalia senegal) is the primary plant source of Gum Arabic (GA), a natural secretion rich in soluble fiber and bioactive polysaccharides. It has longstanding uses in traditional medicine, nutrition, and pharmaceuticals. The present study aimed to evaluate the phytochemical profile, antimicrobial, anti-inflammatory, and anticancer activities of GA methanolic extract (GAME), supported by molecular docking analysis of its key compounds. The gas chromatography–mass spectrometry (GCMS) analysis of the GAME identified many compounds, such as 9-octadecenoic acid (38.29%), methyl ester (15.52), 1,2-benzenedicarboxylic acid, 3-nitro (9.8%), hexadecadienoic acid, methyl ester (8.5), and á-d-mannofuranoside, methyl (7.38). The molecular docking analysis showed that 9-octadecenoic acid had strong binding affinity with target proteins, which included xanthine oxidase (XO), lipoxygenase (LOX), and cyclooxygenase-2 (COX-2), with the highest affinity to XO (−137.03 kcal/mol) and lipoxygenase (−135.09 kcal/mol). GAME possessed broad-spectrum antibacterial activity against Salmonella typhimurium (S. typhimurium), Escherichia coli (E. coli), Pseudomonas aeruginosa (P. aeruginosa), and Staphylococcus aureus (S. aureus), with a zone of inhibition from 16.28 to 16.93 mm. B. subtilis was resistant to the tested extract. The extract also showed good membrane stability and potent inhibition of albumin, XO, LOX, and COX-2, with IC₅₀ values of 31.62, 13.02, 27.6, and 28.99 μg/mL, respectively. The cytotoxic assessment demonstrated moderate, dose-dependent effects on the Caco-2 (colorectal adenocarcinoma) and HeLa (cervical carcinoma) cell lines. These findings highlight the therapeutic potential of GA as a natural plant source of antibacterial, anti-inflammatory and anticancer agents. The combination of molecular docking with in vitro assays provides strong evidence supporting its application in the development of plant-based pharmaceuticals. This research suggests that GA could be a useful ingredient in the creation of anti-inflammatory and antibacterial drugs derived from plants. Full article

Achieving precise control over anticancer drug release remains one of the key challenges in modern pharmaceutical development, as it directly determines therapeutic efficacy, systemic toxicity, and patient outcomes. This review critically evaluates recent advances in three major formulation strategies: polymeric solid dispersions, cyclodextrin-based inclusion complexes, and metal–organic frameworks (MOFs), with a particular focus on their capacity to tailor anticancer drug release. Over the past decade, polymeric solid dispersions and cyclodextrin-based carriers have played a central role in improving the dissolution and bioavailability of poorly water-soluble anticancer agents, while also enabling modified release profiles through rational formulation design. Increasing structural complexity, including ternary systems and supramolecular assemblies, reflects a shift toward more controllable delivery platforms. In recent years, MOFs have emerged as highly adaptable porous materials capable of supporting controlled and stimuli-responsive release. The integration of imaging agents, magnetic components, and photothermal functionalities has further enabled the design of multifunctional and theranostic platforms. Taken together, these technologies reflect a shift from conventional solubility enhancement toward structurally engineered systems designed to achieve predictable and controlled drug release. Continued advances in material design and formulation strategies are expected to further refine release kinetics and support the development of next-generation anticancer therapies aligned with the growing demand for precision medicine. Full article

Background: The growing complexity and cost of oncohematological treatments has created an urgent need for standardized methodologies capable of enabling inter-institutional comparisons of healthcare expenditure within homogeneous patient groups. Cancer-related pharmaceutical costs vary substantially depending on tumour type, disease stage, and therapeutic approach, making cross-institutional benchmarking challenging due to heterogeneity in patient populations and clinical practice patterns. Therefore, integrating cost analysis with clinically meaningful patient stratification is essential to improve resource allocation and outcome evaluation. Methods: A multicentre working group comprising four tertiary hospitals in Madrid (Spain) was established to develop and preliminarily evaluate a novel classification system for adult oncohematological patients. A standardized methodology was designed to stratify patients into homogeneous groups (PATONCO categories) based on tumor location, therapeutic objective, and clinically relevant biomarkers. A cost indicator was defined as the average cost per patient per month for each PATONCO category. Data were extracted from pharmacy dispensing systems and analyzed using descriptive and inferential statistics, including Kruskal–Wallis and post hoc Dunn tests. Results: A total of 3659 patients were included (3168 oncology; 491 hematology), distributed across 62 programmes (54 oncology; 8 hematology). The PATONCOS tool enabled the identification and validation of a cost indicator (average cost/patient/month per category), allowing inter-hospital comparison. Significant differences in costs were observed across most high-prevalence categories, reflecting variability in drug selection within homogeneous patient groups, as documented by the differential use of specific therapeutic agents across centers. The model demonstrated its capacity to detect intra-group homogeneity and inter-group variability, improving the identification of high-cost patient subgroups and supporting benchmarking across centers. Conclusions: The PATONCOS tool provides a novel, clinically oriented stratification methodology that integrates pharmacotherapy, biomarkers, and disease stage with economic evaluation. This approach enables more accurate comparisons of oncology treatment costs between institutions and may support data-driven decision-making in resource allocation. Its implementation may contribute to more sustainable healthcare systems by aligning clinical practice with economic outcomes. Full article

Background/Objectives. Breast cancer is the most frequently diagnosed cancer worldwide, with approximately 15% classified as Triple-Negative Breast Cancer (TNBC). TNBC is characterized by the absence of estrogen receptor (ER) and progesterone receptor (PR), and the lack of HER2 overexpression, limiting use of targeted therapies. Current TNBC treatment relies heavily on chemotherapy, most commonly taxanes including paclitaxel that stabilize microtubules, disrupt chromosome separation and induce apoptosis. TNBCs frequently develop chemoresistance after multiple treatment cycles, highlighting a critical unmet need for novel therapeutic strategies. This study addresses this challenge by targeting salt-inducible kinase 2 (SIK2), which is overexpressed in 85% of TNBCs compared to normal breast tissue. Methodes. In collaboration with Arrien Pharmaceuticals and Greenfire Biologics, we developed ARN-3261/GRN-300, a novel orally bioavailable SIK2 inhibitor and evaluated its ability to sensitize TNBC cells to paclitaxel in vitro and in vivo. Results. GRN-300 demonstrated strong synergy with paclitaxel in all eight TNBC cell lines tested, as indicated by favorable combination indices. In xenograft models, the combination therapy significantly enhanced tumor growth inhibition and prolonged survival compared to either agent alone. Mechanistic studies showed that GRN-300 disrupts the anaphase-promoting complex/cyclosome (APC/C) pathway by downregulating key mitotic regulators, including CDC27, CDK1, and PLK1, thereby potentiating G2/M cell cycle arrest and apoptosis. Conclusions. Together, these findings establish GRN-300 as a promising therapeutic agent that enhances paclitaxel efficacy through complementary disruption of mitotic regulatory pathways, providing strong preclinical rationale for clinical development in TNBC. Full article

Inadequate surface sanitization represents a significant risk to sterility assurance and regulatory compliance. Therefore, an effective cleaning and disinfection program is a critical component of contamination control strategies in pharmaceutical facilities manufacturing sterile medicinal products. This study aimed to standardize a carrier-based methodology for evaluating the efficacy of disinfectants against in-house environmental isolates recovered from a pharmaceutical industry facility. Nine representative strains were selected from five different groups—Gram-positive non-spore-forming bacteria (Micrococcus luteus and Kocuria spp.), Gram-positive spore-forming bacteria (two Bacillus spp. strains), Gram-negative bacteria (Pseudomonas aeruginosa and Acinetobacter haemolyticus), yeasts (Candida parapsilosis and Rhodotorula mucilaginosa), and filamentous fungus (Penicillium spp.)—based on historical environmental monitoring data (2012–2022), and were characterized using matrix-assisted laser desorption/ionization-time-of-flight/mass spectrometry (MALDI-TOF MS) and molecular sequencing (16S rRNA or D2 LSU rDNA). Disinfectant efficacy was assessed on stainless-steel and low-density polyethylene surfaces using NF T 72-281:2014 with adaptations, testing alcohol 70%, sodium hypochlorite 0.5%, quaternary ammonium 0.05%, peracetic acid 0.5%, and accelerated hydrogen peroxide wipes. All agents demonstrated ≥5 log₁₀ reductions against vegetative bacteria and fungi on both surfaces. However, variable sporicidal performance was observed, particularly for one Bacillus cereus group strain (B1342/15), which showed limited viability reduction on stainless steel. These findings highlight inter-strain variability and the greater tolerance of surface-associated spores. The study reinforces the importance of carrier-based testing using in-house isolates to ensure realistic validation of disinfectants and to strengthen microbiological risk management within pharmaceutical contamination control strategies. Full article