Search Results (7,416)

Hop (Humulus lupulus L.) is recognized as a valuable source of bioactive compounds; however, the phytochemical composition and biological potential of wild Romanian hops remain insufficiently characterized. In this study, the bioactive profile of wild hop cones was evaluated using an integrated phytochemical, biological, and in silico approach. The hydroethanolic extract was characterized by a total phenolic content of 25.61 mg GAE/g DW and a total flavonoid content of 3.20 mg RE/g DW, with α-acids predominating (8.77%) and β-acids detected only at trace levels (0.15%). Hydrodistillation yielded 0.613 ± 0.11% essential oil, which was rich in sesquiterpene hydrocarbons (64.61%), mainly α-humulene, β-caryophyllene oxide, selina-3,7-diene, and germacrene B. The hydroethanolic extract exhibited strong antioxidant activity (IC₅₀ = 5.03 µg GAE/mL), whereas the essential oil showed a moderate but dose-dependent radical-scavenging capacity (IC₅₀ = 0.44% v/v). In addition, the essential oil displayed pronounced antibacterial and antibiofilm activity against Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa, at 25 mg/mL, with the highest antibiofilm inhibition observed for Pseudomonas aeruginosa (96.44%). Molecular docking analysis suggested that the major volatile constituents may interact with Staphylococcus aureus Sortase A, providing a plausible mechanistic basis for the observed antibiofilm effects. Overall, these findings indicate that wild Romanian hop cones represent a promising source of antioxidant and antimicrobial bioactive compounds, supporting their potential applications in pharmaceutical, food, and cosmetic formulations, as well as in natural-product-based drug discovery. Full article

The past decade has witnessed an unprecedented transformation in breast cancer management, driven by parallel advances in targeted therapies, immunomodulation, drug-delivery technologies, and molecular diagnostic tools. This review summarizes the key achievements of 2015–2025, encompassing all major biological subtypes of breast cancer as well as technological innovations with substantial clinical relevance. In hormone receptor-positive (HR+)/HER2− disease, the integration of CDK4/6 inhibitors, modulators of the PI3K/AKT/mTOR pathway, oral Selective Estrogen Receptor Degraders (SERDs), and real-time monitoring of Estrogen Receptor 1 (ESR1) mutations has enabled clinicians to overcome endocrine resistance and dynamically tailor treatment based on evolving molecular alterations detected in circulating biomarkers. In HER2-positive breast cancer, treatment paradigms have been revolutionized by next-generation antibody–drug conjugates, advanced antibody formats, and technologies facilitating drug penetration across the blood–brain barrier, collectively improving systemic and central nervous system disease control. The most rapid progress has occurred in triple-negative breast cancer (TNBC), where synergistic strategies combining selective cytotoxicity via Antibody-Drug Conjugates (ADCs), DNA damage response inhibitors, immunotherapy, epigenetic modulation, and therapies targeting immunometabolic pathways have markedly expanded therapeutic opportunities for this historically challenging subtype. In parallel, photodynamic therapy has emerged as an investigational and predominantly local phototheranostic approach, incorporating nanocarriers, next-generation photosensitizers, and photoimmunotherapy capable of inducing immunogenic cell death and modulating antitumor immune responses. A defining feature of the past decade has been the surge in patent-driven innovation, encompassing multispecific antibodies, optimized ADC architectures, novel linker–payload designs, and advanced nanotechnological and photoactive delivery systems. By integrating data from clinical trials, molecular analyses, and patent landscapes, this review illustrates how multimechanistic, biomarker-guided therapies supported by advanced drug-delivery technologies are redefining contemporary precision oncology in breast cancer. The emerging therapeutic paradigm underscores the convergence of targeted therapy, immunomodulation, synthetic lethality, and localized immune-activating approaches, charting a path toward further personalization of treatment in the years ahead. Full article

Bovine mastitis remains a globally prevalent disease, with the limitations of antibiotic-based treatments—such as the rise in antimicrobial resistance and the presence of drug residues—highlighting the urgent need for alternative therapeutic approaches. Inflammation is intricately linked to various cytokines and immunomodulatory proteins, among which cyclophilin A (CypA) serves as a pivotal inflammatory mediator, significantly contributing to the initiation and amplification of inflammatory responses under such conditions. The acquisition of high-purity recombinant protein is a fundamental prerequisite for in vitro functional studies of bovine CypA. This study aimed to construct a eukaryotic expression vector for bovine CypA and verify its expression in CHO-K1 cells. Utilizing the bovine CypA gene sequence available in GenBank, the coding region was artificially synthesized and optimized for codon usage, subsequently being inserted into the pPB[Exp] backbone vector via BsrGI and BstEII double digestion. The resulting polycistronic expression vector contained a CAG promoter driving the CypA transcription, an EF1α promoter driving the EGFP reporter gene, a PGK promoter controlling the puromycin resistance gene, and a C-terminal His-tag. Restriction enzyme digestion and bidirectional Sanger sequencing confirmed that the inserted fragment sequence was completely consistent with the optimized design. Robust EGFP fluorescence was observed 24 h post-transfection and remained stable after puromycin selection. qPCR analysis showed that the Ct value of CypA in the experimental group was 16.20 ± 0.04, while no amplification signal was detected in the control group. Additionally, Western blot analysis identified a CypA-specific band at approximately 18 kDa, confirming the correct expression of the exogenous CypA protein in CHO-K1 cells. Collectively, these results demonstrate the successful construction and validation of a bovine CypA eukaryotic expression vector. The established CHO-K1 expression system exhibited stable and efficient expression, thereby providing a robust foundation for future research on the production and application of recombinant CypA protein. Full article

Background/Objectives: Urine drug testing (UDT) is a core component of nursing interventions within the treatment of substance use disorder (SUD). Beyond the detection of psychoactive substance use and medication adherence, UDT also provides opportunities for therapeutic dialogue, patient support, and recovery monitoring. Despite its routine use, little is known about how patients experience UDT and its potential as a therapeutic nursing tool within recovery-oriented care. This study aimed to explore patients’ lived experiences with UDT to understand its role in recovery-oriented addiction treatment. Methods: A phenomenological study with in-depth, semi-structured interviews was conducted among 12 residents of a supervised living facility at Addiction Care North Netherlands. Data were analyzed using Colaizzi’s seven-step method. Results: Four main themes were constructed in relation to trust within the therapeutic relationship—empowerment, accountability, and autonomy. Patients stated that their perception of UDTs as either supportive or punitive depended strongly on the level of trust within the therapeutic relationship. When trust was present, UDTs were experienced as supportive nursing tools that fostered empowerment and positive self-image, reinforced accountability for recovery goals, and upheld autonomy in decision-making. Conversely, in the absence of trust, UDTs were often perceived as punitive, coercive measures that undermined self-confidence and diminished accountability, ultimately hindering recovery progress. Nursing practices that emphasized nonjudgmental interpretation of results, collaborative decision-making, and patient-centered support contributed to positive experiences. Conclusions: Patients’ experiences indicate that the therapeutic value of UDT is highly dependent on the quality of the patient–nurse relationship. Nurses play a key role in ensuring that UDT is used as a supportive intervention rather than merely a control measure. Integrating UDT into holistic, recovery-oriented care can foster engagement, empowerment, and a sense of accountability. Future research should investigate nursing-led strategies to optimize UDT implementation tailored to treatment phase and patient needs. Full article

We introduce the Onco-Hem Connectome (OHC), a patient similarity network (PSN) designed to organize real-world hemato-oncology inpatients by exploratory phenotypes with potential clinical utility. Background: Polypharmacy and drug–drug interactions (DDIs) are pervasive in hemato-oncology and vary with comorbidity and treatment intensity. Methods: We retrospectively analyzed a 2023 single-center cohort of 298 patients (1158 hospital episodes). Standardized feature vectors combined demographics, comorbidity (Charlson, Elixhauser), comorbidity polypharmacy score (CPS), aggregate DDI severity score (ADSS), diagnoses, and drug exposures. Cosine similarity defined edges (threshold ≥ 0.6) to build an undirected PSN; communities were detected with modularity-based clustering and profiled by drugs, diagnosis codes, and canonical chemotherapy regimens. Results: The OHC comprised 295 nodes and 4179 edges (density 0.096, modularity Q = 0.433), yielding five communities. Communities differed in comorbidity burden (Kruskal–Wallis ${\epsilon }^2$: Charlson 0.428, Elixhauser 0.650, age 0.125, all FDR-adjusted p < 0.001) but not in utilization (LOS, episodes) after FDR (${\epsilon }^2$ ≈ 0.006–0.010). Drug enrichment (e.g., enoxaparin $\Delta$ = +0.13 in Community 2; vinblastine $\Delta$ = +0.09 in Community 3) and principal diagnoses (e.g., C90.0 23%, C91.1 15%, C83.3 15% in Community 1) supported distinct clinical phenotypes. Robustness analyses showed block-equalized features preserved communities (ARI 0.946; NMI 0.941). Community drug signatures and regimen signals aligned with diagnosis patterns, reflecting the integration of resource-use variables in the feature design. Conclusions: The Onco-Hem Connectome yields interpretable, phenotype-level insights that can inform supportive care bundles, DDI-aware prescribing, and stewardship, and it provides a foundation for phenotype-specific risk models (e.g., prolonged stay, infection, high-DDI episodes) in hemato-oncology. Full article

Cytokine and chemokine profiling is central to understanding inflammatory processes and the mechanisms driving diverse diseases. We introduce InCytokine, an open-source tool for semiquantitative analysis of cytokine and chemokine data generated by protein array technologies. InCytokine features robust and modular image-processing workflows, including automated spot detection, template alignment, normalization, quality control measures, and quantitative intensity summarization to deliver consistent and reliable readouts from profiling assays. We evaluated InCytokine by profiling wild-type microglia, TREM2 knockout, and Alzheimer’s disease-associated TREM2 R47H variant cells in response to lipopolysaccharide and sulfatide exposure. Differential expression analysis revealed unique sulfatide-specific and genotype-specific cytokine signatures in TREM2 variants. We also report an intriguing modulation of DPP4 and a divergent expression pattern of ENA-78 in TREM2 variants in response to lipopolysaccharide and sulfatide treatment. Such distinct expression signatures raise the possibility that TREM2 variants may play a role in modulating inflammatory signaling relevant to cardio-metabolic and Alzheimer’s disease. These signatures were corroborated using transcriptional profiling of the same microglia cells, revealing also a good concordance between protein array and RNA sequencing technologies. Taken together, InCytokine is an interactive, user-friendly web application for rapid, reproducible, and scalable analysis of protein array data, proven to generate meaningful insights for drug and biomarker discovery campaigns in pharmaceutical settings. Full article

The SCANVIR^® project is a regional initiative aimed at accelerating the elimination of hepatitis C virus (HCV) by reaching high-risk populations outside traditional healthcare settings. Launched in 2017 in Limoges and later expanded to Poitiers and Bordeaux, the project organized dedicated screening and treatment days in 43 facilities taking care of intravenous drug users, migrants, and prisoners in Nouvelle-Aquitaine. These events involved multidisciplinary teams and advanced diagnostic tools, including rapid tests for HCV, HBV, and HIV; FibroScan^® for liver assessment; and GeneXpert^® for on-site HCV RNA detection. Patients also received counseling on risk prevention, addiction, psychosocial support, and treatment when needed. Between 2017 and 2024, SCANVIR^® screened 1664 patients, with 98.9% accepting FibroScan^®. Anti-HCV antibodies were detected in 23.4% of participants, among whom 41.5% (N = 162) had a replicative profile. Of these, 83% initiated treatment and 80% were cured or were still undergoing therapy. FibroScan^® assessments showed advanced fibrosis in 17% of patients, severe fibrosis in 7.2%, and severe steatosis in 18%. By promoting a “Test, Treat, Prevent” strategy, SCANVIR^® proved cost-effective in diagnosing and treating individuals distant from care structures, highlighting the value of integrating education and prevention into liver disease screening. SCANVIR^® is an officially registered European trademark. Full article

Background: Cardiovascular implications in systemic lupus erythematosus (SLE) are common and varied, including impacts on the pericardium, myocardium, valves, coronary arteries, and conduction system; all of these could be potential substrates or triggers of cardiac arrhythmias by interfering with disease severity and specific medication. Therefore, this narrative review aimed to assess the cardiac involvement in SLE underlying, mainly, cardiac arrhythmias. Methods: We analyzed studies, published between 2015 and 2025 on PubMed, which explore cardiovascular involvement with a focus on arrhythmias in SLE from the perspectives of epidemiology, underlying mechanisms, diagnostic techniques, and the impact of standard and biologic therapies. Results: The cardiac manifestation of LES (lupus pericarditis, lupus myocarditis, Libman–Sacks endocarditis, coronary artery disease, coronary vasculitis or myocardial fibrosis) represents a substrate for arrhythmia risk. These substrates, in association with other arrhythmias mechanisms considered as triggers or conduction abnormalities, determined arrhythmogenic conditions in these patients. In addition to structural heart disease, arrhythmias in SLE are caused by ongoing inflammation, immune system irregularities, microvascular problems, autonomic imbalance, oxidative stress, and side effects from treatments. Despite this complex background, arrhythmias are often overlooked and not routinely investigated in SLE care. Data that show how disease-modifying drugs may affect arrhythmias are limited and inconsistent, highlighting significant gaps in knowledge. Cardiac arrhythmias are a significant but, as yet, insufficiently underrecognized aspect of SLE, with serious implications for prognosis. Conclusions: Systemic lupus erythematosus causes cardiovascular involvement that is associated with arrhythmias through various and complexes mechanisms, mainly related to direct cardiovascular structural damage, systemic inflammation or specific therapies. Data on arrhythmias secondary to cardiovascular damage in patients with SLE in the literature are limited. Therefore, early detection of electrical issues, regular cardiovascular evaluation in high-risk patients, and careful management of treatment effects are vital. A coordinated, multidisciplinary cardio-rheumatology approach is essential to improving arrhythmia detection, tailoring treatments, and ultimately decreasing cardiovascular complications and deaths in SLE patients. Full article

Background and Objectives: Epilepsy is a chronic neurological disorder characterized by recurrent seizures caused by abnormal brain activity. Reliable near-real-time seizure detection is essential for preventing injuries, enabling early interventions, and improving the quality of life for patients with drug-resistant epilepsy. This study presents a near-real-time epileptic seizure detection framework designed for low-latency operation, focusing on improving both clinical reliability and patient comfort through electrode reduction. Method: The framework integrates bidirectional long short-term memory (BiLSTM) networks with wavelet-based feature extraction using Electroencephalogram (EEG) recordings from the EPILEPSIAE dataset. EEG signals from 161 patients comprising 1032 seizures were analyzed. Wavelet features were combined with raw EEG data to enhance temporal and spectral representation. Furthermore, electrode reduction experiments were conducted to determine the minimum number of strategically positioned electrodes required to maintain performance. Results: The optimized BiLSTM model achieved 86.9% accuracy, 86.1% recall, and an average detection delay of 1.05 s, with a total processing time of 0.065 s per 0.5 s EEG window. Results demonstrated that reliable detection is achievable with as few as six electrodes, maintaining comparable performance to the full configuration. Conclusions: These findings demonstrate that the proposed BiLSTM-wavelet approach provides a clinically viable, computationally efficient, and wearable-friendly solution for near-real-time epileptic seizure detection using reduced EEG channels. Full article

Background/Objectives:Pyrus ussuriensis Maxim. has been cultivated in many regions worldwide. This plant is also regarded as a profitable fruit crop for the development of many food and functional products. There is limited research on the application of the LC-MS associated reaction method for screening active compounds. In this study, we developed an analytical technique employing an ultra-high-performance liquid chromatography-electrospray ionization-tandem mass spectrometry (UHPLC-ESI-MS/MS) system. Methods: The metabolite annotation procedure was used to interpret and validate data analysis via spectral matching against public databases. Results: As a result, metabolites from P. ussuriensis water and EtOH extracts were identified, and their quantities were further evaluated. The established method was employed to determine antioxidant capacity using a pre-incubation UHPLC-2,2-diphenyl-1-picrylhydrazyl (DPPH) assay, thereby identifying antioxidant ingredients. The antioxidative interference of active constituents was predicted by calculating the decrease in the peak areas of the chemical composition detected in chromatograms between treated and non-treated samples. Furthermore, drug-likeness was also assessed via pharmacokinetics (absorption, distribution, metabolism, and excretion: ADME) evaluation. Conclusions: The online UHPLC-MS-DPPH method would be a powerful tool for the rapid characterization of antioxidant ingredients in plant extracts. The current study highlights the value of P. ussuriensis for improved health benefits. Full article

The first major HIV outbreak in the Eastern Europe and Central Asia (EECA) region was registered. Phylogeographic analysis revealed that the main exporters of the virus were Donetsk and Lugansk, from which most migration events occurred, and the predominant genetic variant in Donetsk was subtype A. However, despite a relatively high level of understanding of HIV genetic diversity, data on resistance mutations remain limited. The aim of this study is to assess HIV genetic diversity and drug resistance in Donetsk, Luhansk and Zaporizhzhia regions. A comprehensive examination was conducted, encompassing 392 sequences covering the integrase-coding region of the HIV-1 pol gene. Subtyping was achieved through various programs, including COMET, the Stanford Database, BLAST and REGA. The study also involved phylogenetic analysis to clarify HIV genovariants. The profiles and levels of drug resistance were determined. The overall prevalence of drug resistance mutations to the integrase strand transfer inhibitors (INSTIs) among the studied patients was 3.6% (95% CI, 1.7–5.4%). The most commonly detected major DRMs for INSTIs were G140R (4, 28.6%) and Y143R (3, 21.4%), followed by R263K (2, 14.3%), G140RG (2, 14.3%), Y143YS (2, 14.3%), Y143YC (1, 7.1%) and Q148QR (1, 7.1%). A high-level resistance was observed for RAL—8/14 (57.1%), CAB—6/14 (42.9%) and EVG—2/14 (14.3%). The results presented are part of a further larger study and are preliminary. The results of this study suggest a moderate HIV-1 resistance situation in the Donetsk, Luhansk and Zaporizhzhia regions, but require further monitoring. Full article

The unique physicochemical properties of gold nanoparticles (GNPs) have made them versatile tools for biomedical applications, such as imaging, therapy, and drug delivery. The surface modification of GNPs with polymers or biomolecules can enhance their colloidal stability and facilitate internalization into cells. However, the efficient and biocompatible delivery to the central nervous system remains a major challenge, as many existing nanocarriers show poor capacity to cross the blood-brain barrier. We developed a method to coat GNPs with linear polyethyleneimine (GNP@PEI) through a chemical reduction bottom-up approach, in which linear PEI hydrochloride acts simultaneously as a reducing and stabilizing agent of colloidal dispersion. This strategy yielded monodisperse spherical GNP@PEI nanoparticles with an average diameter of 50 nm. The physicochemical profile, biocompatibility, and capacity for neural uptake of this potentially brain-targeted nanoplatform were then evaluated. GNP@PEI nanoparticles exhibited high biocompatibility in several primary neural cultures and cell lines, with cellular uptake showing clear cell-type-dependent differences. In vivo studies carried out in a murine model demonstrated that after the intranasal or intraperitoneal administrations of GNP@PEI nanoparticles, detectable levels of gold were found in several organs, including the brain. Collectively, these findings highlight the potential of GNP@PEI as a promising nanoplatform for brain-targeted delivery and for advancing the development of therapeutic strategies for neurological disorders. Full article

Mycoplasma synoviae (MS) is a major pathogen threatening China’s poultry industry, causing severe economic losses, and clarifying its epidemiology is pivotal for disease control and flock purification. In this study, a total of 3215 chicken samples collected from 643 broiler farms across 15 provinces in China in 2024 were analyzed. PCR detected 14% positivity (450 samples), and 18 isolates obtained from these positive samples (4.0% isolation rate). Multilocus sequence typing (MLST, 7 housekeeping genes) and neighbor-joining phylogenetic analysis (integrating 425 reference sequences from public databases) identified 13 distinct sequence types (STs), demonstrating considerable genetic diversity among circulating MS strains. Pathogenicity assessment of the five isolates revealed that the infected chickens exhibited varying degrees of infectious synovitis, while no respiratory signs were observed. In addition, antimicrobial susceptibility testing against 10 commonly used antibiotics was conducted on the 18 strains, providing urgently needed guidance for rational drug use in the clinical treatment of both breeder and broiler flocks. This large-scale epidemiological study yields crucial insights into the current prevalence and genetic diversity of MS in China and lays a scientific foundation for formulating targeted prevention strategies and optimizing management practices. Full article

Background: Medication adherence and persistence in treating chronic diseases present as a continuous challenge for healthcare providers in long-term management. The most frequent reasons that several diseases are poorly controlled in the population include suboptimal drug adherence and discontinuation of therapies. One main issue why physicians cannot detect patients with poor adherence is that they have relatively limited time and tools to do so. Aim: To review the critical role of medication adherence in the management of chronic diseases by addressing the following: what medication adherence is; its critical role; factors and strategies influencing it; challenges and consequences of poor adherence; patients at risk; present and future strategies in place to detect and improve adherence; implications for public health and health value creation for patients; key analytical frameworks for understanding it; determinants; how adherence improves health; the role of healthcare professionals and technological innovations; implications of medication adherence; adherence as a key area for exploring the psychological mechanisms underlying patient behavior; and patient adherence as a major social and public health challenge. Finally, this review considers strengths, limitations, recommendations, and future value. Methodology: The following databases were used to carry out the review: PubMed, Scopus, Google Scholar, and ScienceDirect. The following themes were combined in the search: what adherence is, why it is critical, why adherence occurs, and how to improve adherence. The following search terms were used: what adherence is and critical, why and adherence and occurs, and how and to improve adherence. Results: Under the theme of why adherence is critical, five sub-themes were reviewed; four sub-themes were reviewed under the theme of why adherence occurs; and five sub-themes were reviewed under the theme of how to improve adherence. Conclusions: Strategies to enhance medication adherence involve a comprehensive approach that includes patient education, streamlined treatment plans, digital tools, and effective communication from healthcare professionals. Full article

Reversed-phase high-performance liquid chromatography (RP-HPLC) remains one of the most widely applied analytical techniques in the development and quality control testing of finished pharmaceutical products. The combination of gradient chromatographic methods with diode-array detection (DAD) enhances selectivity, ensuring accuracy and reliability when testing drugs with diverse chemical properties in a single dosage form (i.e., fixed-dose combination (FDC) products). In this study, an RP-DAD-HPLC method was developed for the quantitative analysis of clofazimine (CFZ) and pyrazinamide (PZA) for inclusion in an FDC topical drug delivery system. Chromatographic separation was achieved using a C18 column (4.6 mm × 150 mm, 5 µm particle size) with gradient elution at 1 mL/min, employing 0.1% aqueous formic acid and acetonitrile (mobile phases). PZA and CFZ were detected at 254 nm and 284 nm, respectively. The method was validated in accordance with ICH Q2 guidelines, assessing specificity (considering interference from solvents, product matrix, and degradation products), linearity (7.8–500.0 µg/mL, r² = 0.9999), system repeatability (%RSD ≤ 2.7%), and intermediate precision (25–500 µg/mL, %RSD ≤ 0.85%). Method robustness was evaluated using a three-level Box–Behnken design (BBD) with response surface methodology (RSM) to assess the effects of variations in detection wavelength, mobile phase flow rate, and column temperature. Full article