Search Results (1,163)

Phthalocyanines (Pcs) are well-established photosensitizers in photodynamic therapy, valued for their strong light absorption, high singlet oxygen generation, and photostability. Recent advances have focused on covalently conjugating Pcs, particularly zinc phthalocyanines (ZnPcs), with a wide range of small bioactive molecules to improve selectivity, efficacy, and multifunctionality. These conjugates combine light-activated reactive oxygen species (ROS) production with targeted delivery and controlled release, offering enhanced treatment precision and reduced off-target toxicity. Chemotherapeutic agent conjugates, including those with erlotinib, doxorubicin, tamoxifen, and camptothecin, demonstrate receptor-mediated uptake, pH-responsive release, and synergistic anticancer effects, even overcoming multidrug resistance. Beyond oncology, ZnPc conjugates with antibiotics, anti-inflammatory drugs, antiparasitics, and antidepressants extend photodynamic therapy’s scope to antimicrobial and site-specific therapies. Targeting moieties such as folic acid, biotin, arginylglycylaspartic acid (RGD) and epidermal growth factor (EGF) peptides, carbohydrates, and amino acids have been employed to exploit overexpressed receptors in tumors, enhancing cellular uptake and tumor accumulation. Fluorescent dye and porphyrinoid conjugates further enrich these systems by enabling imaging-guided therapy, efficient energy transfer, and dual-mode activation through pH or enzyme-sensitive linkers. Despite these promising strategies, key challenges remain, including aggregation-induced quenching, poor aqueous solubility, synthetic complexity, and interference with ROS generation. In this review, the examples of Pc-based conjugates were described with particular interest on the synthetic procedures and optical properties of targeted compounds. Full article

Biotechnological research increasingly focuses on developing new drugs to counter the rise of antibiotic-resistant strains in hospitals. This study aimed to create bacterial lysates from antibiotic-resistant pathogens isolated from patients and medical instruments across hospital departments. Identification was performed based on morphological, cultural, and biochemical characteristics, as well as 16S rRNA gene sequencing using the BLAST algorithm. Strain viability was assessed using the Miles and Misra method, while sensitivity to eight antibacterial drug groups and biosafety between cultures were evaluated using agar diffusion. From 15 clinical sources, 25 pure isolates were obtained, and their phenotypic and genotypic properties were studied. Carbohydrate fermentation testing confirmed that the isolates belonged to the genera Escherichia, Citrobacter, Klebsiella, Acinetobacter, Pseudomonas, Staphylococcus, Haemophilus, and Streptococcus. The cultures exhibited good viability (10⁹–10¹⁰ CFU/mL) and compatibility with each other. Based on prevalence and clinical significance, three predominant hospital pathogens (Klebsiella pneumoniae 12 BL, Pseudomonas aeruginosa 3 BL, and Acinetobacter baumannii 24 BL) were selected to develop a bacterial lysate consortium. Lysates were prepared with physical disruption using a French press homogenizer. The resulting product holds industrial value and may stimulate the immune system to combat respiratory pathogens prevalent in Kazakhstan’s healthcare settings. Full article

This study was undertaken to identify foodborne bacteria and fungi from different parts of eggs depending on their storage duration, organoleptic properties, total viable count, and antibiotic resistance profile. Thirty-two samples were randomly collected from commercial layer farms in Mymensingh. Following the protocol of sample preparation, outer-surface and inner-content samples were streaked onto various selective media. Isolation and identification were carried out by observing Gram staining and biochemical properties. Molecular detection was confirmed through a PCR assay using specific primers for Salmonella spp., E. coli, Staphylococcus spp., and fungus (Simplicillium spp. and Saccharomyces spp.). To determine the antibiotic resistance profile, the disk diffusion method was followed against nine antibiotic disks. The isolation rate of E. coli, Salmonella spp., and Staphylococcus spp. was 53.13%, 40.63%, and 40.63%, respectively, in the outer eggshell and 15.63%, 25%, and 15.63%, respectively, in the inner content of the eggs. Regarding the fungus content (yeast and mold), 100% was obtained in the outer eggshell, whereas there was an absence of fungus in the inner content. It was observed that all the isolates of E. coli, Salmonella spp., and Staphylococcus spp. were highly sensitive to either Ciprofloxacin or Levofloxacin and extremely resistant to Amoxicillin or Azithromycin drug disks or both. The data also shows that storage duration had a proportional relationship with TVC and an inversely proportional relationship with organoleptic properties. This study indicates that eggs harbor multidrug-resistant foodborne bacteria, which might constitute a public health hazard if these antibiotic-resistant bacteria are transferred to humans. Full article

The concept of “platinum sensitivity” has long guided prognostic assessment and treatment selection in recurrent ovarian cancer. However, the emergence of targeted agents, such as bevacizumab and poly (ADP-ribose) polymerase inhibitors, has complicated its clinical utility. In contrast, emerging evidence suggests that platinum sensitivity may also be applicable to recurrent endometrial cancer. As in ovarian cancer, a prolonged platinum-free interval (PFI) in recurrent endometrial cancer is associated with an improved efficacy of subsequent platinum-based chemotherapy. The PFI is linearly correlated with the response rate to platinum re-administration, progression-free survival, and overall survival. Patients are typically classified as having platinum-resistant or platinum-sensitive disease based on a PFI cutoff of 6 or 12 months. However, unlike in ovarian cancer—where the duration of response to second-line platinum-based chemotherapy rarely exceeds the prior PFI (~3%)—approximately 30% of patients with recurrent endometrial cancer exhibit a sustained response to platinum rechallenge that extends beyond their preceding PFI. Despite the incorporation of immune checkpoint inhibitors into the treatment landscape of endometrial cancer, the role of platinum sensitivity in clinical decision-making—particularly regarding treatment sequencing and drug selection—remains a critical and unresolved issue. Further research is warranted to elucidate the mechanisms underlying platinum resistance and to guide optimal therapeutic strategies. Full article

Aquatic biomass—ranging from fish scales and crustacean shells to various algae species—offers an abundant, renewable source for carbon dot (CD) synthesis, aligning with circular economy principles. This review highlights recent studies for valorizing aquatic biomass into high-performance carbon-based nanomaterials—specifically aquatic biomass-based carbon dots (AB-CDs)—briefly summarizing green synthesis approaches (e.g., hydrothermal carbonization, pyrolysis, and microwave-assisted treatments) that minimize environmental impact. Subsequent sections highlight the varied applications of AB-CDs, particularly in biosensing (including the detection of marine biotoxins), environmental monitoring of water pollutants, and drug delivery systems. Physically AB-CDs show unique optical and physicochemical properties—tunable fluorescence, high quantum yields, enhanced sensitivity, selectivity, and surface bio-functionalization—that make them ideal for a wide array of applications. Overall, the discussion underlines the significance of this approach; indeed, transforming aquatic biomass into carbon dots can contribute to sustainable nanotechnology, offering eco-friendly solutions in sensing, environmental monitoring, and therapeutics. Finally, current challenges and future research directions are discussed to give a perspective of the potential of AB-CDs; the final aim is their integration into multifunctional, real-time monitoring and therapeutic systems—for sustainable nanotechnology innovations. Full article

Background/Objectives: Temozolomide is an important drug used for the treatment of glioblastoma multiforme. Covalent conjugation of temozolomide to triplex-forming oligonucleotides could facilitate better sequence discrimination when targeted to DNA to lessen off-target effects and potentially reduce side-effects associated with conventional chemotherapy. The base sensitivity of temozolomide precludes use of basic deprotection conditions that typify the solid-supported synthesis of oligonucleotides. Methods: A novel di-iso-propylsilylene-linked solid support was developed and used in solid-supported synthesis of oligonucleotide conjugates. Results: Conditions were established whereby fully deprotected, solid-supported oligonucleotides could be prepared for derivatisation. Cleavage of the di-iso-propylsilylene linker was possible using mild, acidic conditions. Conclusions: The di-iso-propylsilylene-linked solid support was developed and shown to be compatible with base-sensitive oligonucleotide conjugate formation. The DNA triplex formation exhibited by a temozolomide oligonucleotide conjugate was equal in stability to the unconjugated control, opening new possibilities for sequence selective delivery of temozolomide to targeted DNA. Full article

Pancreatic ductal adenocarcinoma (PDAC) tumors exhibit pronounced phenotypic plasticity, alternating between a treatment-sensitive classical phenotype and a more aggressive basal-like state associated with drug resistance and poor prognosis. The frequent coexistence of these phenotypes complicates patient stratification and the selection of effective therapies. Tumor-derived organoids are valuable tools for drug screening; however, their clinical relevance relies on how accurately they recapitulate the phenotypic and functional characteristics of the original tumors. In this study, we present a quantitative analysis of how hydrogel composition influences the phenotype, tissue remodeling, metabolism, and drug resistance of PDAC organoids. Organoids were cultured within three types of hydrogels: Matrigel, collagen-I, and a mixture of collagen-I and Matrigel. Our results demonstrate that: (i) PDAC organoids grown in Matrigel exhibit a classical phenotype, with metabolic and drug response profiles similar to those of low-physiological two-dimensional cultures; (ii) Organoids grown in collagen-containing hydrogels, particularly those in collagen-Matrigel composites, faithfully recapitulate basal-like tumors, characterized by epithelial-to-mesenchymal transition, tissue remodeling, metabolic activity, and drug resistance; (iii) TGFβ induces an exacerbated, highly invasive basal-like phenotype. Summarizing, our findings highlight the importance of 3D hydrogel composition in modulating PDAC organoid phenotype and behavior and suggest collagen-Matrigel hydrogels as the most suitable matrix for modeling PDAC biology. Full article

Cellular and molecular characteristics of the tumor microenvironment are fundamental for the formation of niches. These structures include both cellular and matrix components and have been shown to protect and promote cancer formation and progression. The peculiarities of tumor niches have been suggested by many authors as targets with high therapeutic potential. This narrative review analyzes the chemical characteristics of the tumor microenvironment and describes experimental and clinical approaches to influence its contribution to cancer promotion and the spread of metastases. In particular, the possible chemical differences, like pH, oxygen levels, and cell composition, to be used for the design of drugs or the delivery of antiproliferative moieties for a more precise oncology approach, will be discussed. The literature proposes a vast number of molecules, but this review focuses on hypoxia-activated molecules, pH-sensitive nanocarriers, metal-based drugs, and gasotransmitters targeting selectively the tumor microenvironment as possible negative modulators of the contribution of niches to tumor promotion. The chemical peculiarities of the tumor niche are discussed for possible pharmacological developments. Full article

Background: Tumors of the pleura, such as metastatic lung cancer and mesothelioma, are amongst the most lethal and therapy-resistant tumors. The first manifestation of the disease is often pleural effusion, the first available material for diagnosis. The five-year survival rate is exceptionally low, around 10–20%, and only a small proportion of patients harbor mutations that allow targeted treatments. Almost all patients develop resistance to treatment, which is often palliative. There is therefore an urgent need to refine the selection of drugs and patients for personalized treatment. Methods: We isolated and cultured cells from pleural effusions in 3D cell aggregates and compared their drug sensitivity ex vivo to the clinical response to the same chemotherapeutic agents, combined with targeted sequencing and network analysis. Results: The ex vivo drug response showed a positive correlation with the treatment response and survival of patients in the clinic, with a stronger link to overall survival than to progression-free survival. Cryopreserved cells showed a similar response to freshly collected cells from the clinic. Conclusions: The findings advance the field of ex vivo screening and present an opportunity to combine strategies for functional precision medicine with comprehensive characterization of disease for improved treatment and future management of lung cancer. Full article

Objective: Radical therapies are associated with significant morbidity in patients with localized prostate cancer (PCa). While advances in nuclear magnetic resonance techniques have enabled the development of focal ablation procedures that can selectively destroy tumors, preserve the gland and surrounding structures, and minimize side effects, existing vascular-targeted photodynamic therapy (VTP) and nanodrug therapies often face limitations, such as recurrence and insufficient drug concentration at the tumor site. This study investigated a novel approach that combines VTP with systemic treatment using drug-loaded nanoparticles in a murine model, demonstrating substantial advancements beyond current monotherapies. Methods: SCID (severe combined immunodeficiency) mice were engrafted with androgen-sensitive prostate tumor cells (LNCaP-AR) and treated with a combination of VTP and two different drugs linked to fucoidan nanoparticles (Enzalutamide and Paclitaxel). Experiments were performed using different cohorts: the evaluation of oncological effect, the administration time and concentration of systemic therapy, a comparison of efficacy between VTP and radiotherapy, and the induction of the abscopal effect in untreated synchronous tumors. Results: The groups that received combination therapy showed better tumor control. After eight weeks, the recurrence-free survival rates were 87.5%, 62.5%, and 50% in the VTP + N-PAC, VTP + N-ENZ, and VTP monotherapy groups, respectively (p < 0.05). There was a significant difference in the intra-tumoral concentration of nanodrugs between the groups with combined treatment and monotherapy. After two weeks, the monotherapy groups showed almost total elimination of the drugs, whereas in the combined therapy groups, this concentration remained high, starting to decrease after three weeks (p < 0.05). Treatment with nanodrugs associated with VTP showed superior oncological benefits compared to radiotherapy alone or in combination with other therapies. The abscopal effect on synchronous tumors was not demonstrated with VTP alone or in combination with nanodrugs. Conclusions: Combining vascular photodynamic therapy with nanodrugs was highly effective in treating a prostate tumor model, leading to increased survival and a reduced risk of tumor recurrence. This approach significantly advances beyond existing VTP and nanodrug therapies by improving tumor control, ensuring sustained intra-tumoral drug concentration, and yielding superior oncological outcomes. Our results suggest that this therapy is a potential treatment option for prostate tumors treated with VTP in future clinical trials. Full article

Aminoglycoside antibiotics are critical in clinical use for treating severe infections, but they can occasionally cause irreversible sensorineural hearing loss. To establish a rational pathway for otoprotectant discovery, we provide an integrated, three-tier methodology—comprising cell-model selection, transcriptomic analysis, and a gentamicin–Texas Red (GTTR) uptake assay—to guide the development of otoprotective strategies. We first utilized two murine auditory cell lines—UB/OC-2 and HEI-OC1. We focused on TMC1 and OCT2 and further explored the underlying mechanisms of ototoxicity. UB/OC-2 exhibited a higher sensitivity to gentamicin, which correlated with elevated OCT2 expression confirmed via RT-PCR and Western blot. Transcriptomic analysis revealed upregulation of PI3K-Akt, calcium, and GPCR-related stress pathways in gentamicin-treated HEI-OC1 cells. Protein-level analysis further confirmed that gentamicin suppressed phosphorylated Akt while upregulating ER stress markers (GRP78, CHOP) and apoptotic proteins (cleaved caspase 3, PARP). Co-treatment with PI3K inhibitors (LY294002, wortmannin) further suppressed Akt phosphorylation, supporting the role of PI3K-Akt signaling in auditory cells. To visualize drug entry, we used GTTR to evaluate its applicability as a fluorescence-based uptake assay in these cell lines, which were previously employed mainly in cochlear explants. Sodium thiosulfate (STS) and N-acetylcysteine (NAC) significantly decreased GTTR uptake, suggesting a protective effect against gentamicin-induced hair cell damage. In conclusion, our findings showed a complex ototoxic cascade involving OCT2- and TMC1-mediated drug uptake, calcium imbalance, ER stress, and disruption of PI3K-Akt survival signaling. We believe that UB/OC-2 cells serve as a practical in vitro model for mechanistic investigations and screening of otoprotective compounds. Additionally, GTTR may be a simple, effective method for evaluating protective interventions in auditory cell lines. Overall, this study provides molecular-level insights into aminoglycoside-induced ototoxicity and introduces a platform for protective strategies. Full article

The analysis of wastewater is essential in environmental chemistry, particularly for monitoring emerging contaminants and assessing ecological impacts. In this context, hyphenated chromatographic techniques are widely used, with liquid chromatography being one of the most common. However, gas chromatography coupled with mass spectrometry (GC-MS) remains a valuable tool in this field due to its sensitivity, selectivity, and widespread availability in most laboratories. This review examines the application of validated methods for wastewater analysis using GC-MS (MS), highlighting its relevance in identifying micropollutants such as pharmaceuticals, drugs of abuse, pesticides, hormones, and industrial by-products. The validation of analytical methods is crucial to ensuring the reliability and reproducibility of data and the accurate monitoring of contaminants. Key parameters, including sample volume, recovery efficiency, and detection and quantification limits, are discussed, evaluating different approaches to optimising the identification of different classes of contaminants. Additionally, this study explores advances in sample preparation techniques, such as solid-phase microextraction (SPME), dispersive liquid–liquid microextraction (DLLME), and solid-phase extraction (SPE), which enhance efficiency and minimise interferences in the analysis. Finally, future perspectives are discussed, including the integration of emerging technologies such as high-resolution mass spectrometry, the miniaturisation of GC systems, and the development of faster and more sustainable analytical methods. Full article

Polycystic ovary syndrome (PCOS) is an endocrine disorder prevalent in women of reproductive age, often requiring complex pharmacological management. The heterogeneity of the syndrome and the use of on- and off-label therapeutic agents—ranging from insulin sensitizers and ovulation inducers to oral contraceptives and herbal supplements—pose significant challenges, including adverse effects, drug interactions, and poor adherence. This narrative review explores the role of pharmacists in identifying and mitigating drug-related problems (DRPs) associated with PCOS therapy. Through thematic synthesis of the current literature, the study highlights common DRPs such as suboptimal drug selection, inappropriate dosing, prolonged therapy duration, and treatment-related safety concerns. It underscores the value of pharmacists’ interventions in enhancing medication adherence, optimizing therapeutic regimens, providing patient education, and monitoring adverse events. A structured, patient-level pharmaceutical care model is proposed, emphasizing personalized assessment, interdisciplinary collaboration, and continuous follow-up. The integration of clinical pharmacists into PCOS care teams has the potential to improve treatment effectiveness, patient satisfaction, and long-term health outcomes. Pharmacists’ contributions are especially critical given the widespread use of off-label therapies and supplements with variable evidence of benefit. Tailored pharmaceutical care can thus bridge the existing gaps in PCOS management and enhance the quality of life for the affected individuals. Full article

In the present study, a quantitative analysis of culturable microflora of car cabin filters was accomplished, with a special focus on bacteria resistant to some antibiotics. The occurrence of antibiotic-resistant bacteria was considered in the filters with activated carbon and filters with antibacterial properties. The minimum inhibitory concentration was evaluated for selected bacterial strains isolated from the filters. It was found that cabin filters after long-time operation are not only heavily contaminated with bacteria and fungi but also constitute a habitat for numerous antibiotic-resistant bacteria. The numbers of culturable bacteria resistant to penicillin, nitrofurantoin, rifampicin, doxycycline, or gentamicin reached 10²–10³ CFU/g of filter material. No relationship was observed between car brand or filter type and the abundance of antibiotics-resistant bacteria. The lower bacterial content of antibacterial filters was not accompanied by a proportionally lower content of resistant microorganisms which may indicate that the present techniques are not sufficient to limit their growth effectively. Pseudomonas sp. isolates from the filter material were not sensitive even in relation to high concentrations of some antibiotics, which confirms their significant resistance potential and may be important in the context of the spread of drug resistance in the vehicles indoors. Full article

Background: “CFTR modulators” (also named “caftor”) have been developed and introduced into clinical practice to improve the functionality of defective CFTR protein. Therapeutic drug monitoring (TDM) is not currently used for CFTR modulators in routine clinical practice and there is still much to learn about the pharmacokinetic/pharmacodynamic (PK/PD) and the safety profiles of these drugs in a real-world setting. Moreover, therapeutic ranges are not yet available for both pediatric and adult cystic fibrosis (CF) patients. Methods: A new and sensitive liquid chromatography tandem mass spectrometry (LC-MS/MS) method for contemporary quantification of ivacaftor (IVA), tezacaftor (TEZ) and elexacaftor (ELX) in plasma samples has been developed and validated. The clinical performance of our method has been tested on samples collected during the routine clinical practice from n = 25 pediatric patients (aged between 7 and 17 years) affected by cystic fibrosis. This LC-MS/MS method has been validated according to ICH (International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use) guidelines for the validation of bioanalytical methods. Results: Our method fulfilled ICH guidelines in terms of accuracy, precision, selectivity, specificity and carry-over. Intra- and inter-day accuracy and precision were ≤15%. The 9-day autosampler stability was 90–100% for TEZ and ELX; meanwhile, it fell to 76% for IVA. An injection volume of 1 µL and a wider quantification range (0.1–20 µg/mL) represent a novelty of our method in terms of sensitivity and fields of application. Finally, the evaluation of PK exposure parameters for IVA revealed strong agreement with previously published reports and with results from the summary of product characteristics (SmPCs). Conclusions: This method could be adopted to contemporarily measure ELX/TEZ/IVA plasma levels for both PK studies and monitor therapy compliance, especially in case of poor or partial responses to treatment, or to evaluate drug–drug interactions when multiple concomitant medications are required. Considering also the high cost burden of these medications to the health system, a TDM-based approach could facilitate more cost-effective patient management. Full article