Abstract: Kynurenic acid (KYNA), a putative neuroprotective agent, modulates glutamatergic pathways in Schizophrenia and Parkinson’s Disease but is limited by acute motor activity impairments (e.g., ataxia). Research leveraging animal disease models explores its structure-activity relationship to enhance therapeutic efficacy while mitigating adverse effects, addressing global neuropsychiatric disorders affecting over 1 billion people. Structural analogs of KYNA (SZR-72, SZR-73, and SZR-81) were designed to uncouple therapeutic benefits from motor toxicity, yet systematic comparisons of their acute behavioral profiles remain unexplored. Here, we assess the motor safety, time-dependent effects, and therapeutic potential of these analogs in mice. Using acute intracerebroventricular dosing, we evaluated motor coordination (rotarod), locomotor activity (open-field), and stereotypic behaviors. KYNA induced significant ataxia and stereotypic behaviors at 15 minutes, resolving by 45 minutes. In contrast, all analogs avoided acute motor deficits, with SZR-73 maintaining baseline rotarod performance and eliciting a delayed decrease in ambulation and inquisitiveness in open-field assays. These findings demonstrate that structural optimization of KYNA successfully mitigates motor toxicity while retaining neuromodulatory activity. Here we show that SZR-73 emerges as a lead candidate, combining transient therapeutic effects with preserved motor coordination. This study advances the development of safer neuroactive compounds, bridging a critical gap between preclinical innovation and clinical translation. Future work must validate chronic efficacy, disease relevance, and mechanistic targets to harness the full potential of KYNA analogs in treating complex neuropsychiatric disorders.

Abstract: Multiple sclerosis (MS) is a chronic inflammatory and neurodegenerative disease. Repetitive demyelination defeats remyelination and impairs axonal conduction thus resulting in the characteristic disabilities of MS. Therefore, reducing demyelination and promoting remyelination are key strategies for the prevention and treatment of MS. In searching for new drugs to treat MS, many traditional Chinese herbs are gaining increasing attention. In the present study, baicalein (BA) was comprehensively investigated, by examining its effects on the cuprizone (CPZ)-induced neuropathological changes and behavioral abnormalities which are reminiscent of the clinical symptoms of MS patients, and exploring the cellular and molecular mechanisms underlying the effects. Our in vivo experiments demonstrated that BA facilitates the recovery of motor and cognitive impairment in CPZ-exposed mice while promoting the remyelination process and inhibiting neuroinflammation in their brains. Underlying these protective effects, BA intervention prevented the nuclear factor erythroid 2-related factor 2 (NRF2) and its downstream antioxidant enzymes (HO-1, NQO1, and SOD2) from over activation, thereby maintaining the signal pathway at normal levels through its antioxidant actions. Our in vitro experiments provided evidence that both CPZ and H2O2 delay the development of oligodendrocyte (OL) lineage cells by damaging mitochondria of the cells and resulting in oxidative stress. In the absence of astrocytes and microglia, BA effectively prevented cultured OLs from development delay by scavenging ROS resulted from damaged mitochondria of the cells. The elucidation of these cellular and molecular mechanisms will prompt clinical application of more naturally derived compounds with antioxidant properties to treat patients with MS.

Abstract: The C-C motif chemokine receptor 1 (CCR1) is widely expressed in various immune cells and plays crucial roles in the maturation and migration of immune cells. CCR1 has been considered an attractive drug target for treating allergic and autoimmune diseases. An anti-mouse CCR1 (mCCR1) monoclonal antibody (clone S15040E) has been used in various in vivo studies to identify mCCR1-positive cells by flow cytometry. However, the binding epitope has not been determined. This study investigated the binding epitope of S15040E using flow cytometry. The mCCR1 extracellular domain-substituted mutant analysis showed that S15040E recognizes the extracellular loop 2 (ECL2, aa 172–197) of mCCR1. Next, alanine (or glycine) scanning was conducted in the ECL2 region. The results revealed that the Trp176, Phe178, Arg181, and Cys183 are essential amino acids for the recognition by S15040E. These results showed the involvement of the ECL2 of mCCR1 in the recognition by S15040E.

Abstract: Insomnia is the most prevalent sleep disorder, estimated to affect at least one-third of the global population. There are a variety of treatment options available for both acute and chronic insomnia. Currently, the pharmacological arsenal for treating insomnia includes short- or intermediate-acting benzodiazepine hypnotics, non-benzodiazepine hypnotic sedatives, melatonin receptor agonists, and sedating antidepressants. Diphenhydramine, a first-generation antihistamine, is commonly used in the treatment of allergies and dermatitis. This review examines the preclinical and clinical efficacy and safety evidence of diphenhydramine in treating short-term insomnia. Additionally, it provides expert consensus on its implementation as an over-the-counter medication for this condition. The available evidence indicates that diphenhydramine is an effective treatment for acute insomnia in adults, offering a safe, and affordable option for most patients suffering from this condition. Experts concur that there is strong evidence supporting the recommendation of diphenhydramine for the treatment of acute insomnia in adults.

Abstract: This retrospective observational study evaluates Alabama’s Coronavirus Disease 2019 (COVID-19) vaccine distribution plan and examines potential socioeconomic disparities of the distribution.COVID-19 vaccine distribution data from December 15, 2020, to March 25, 2022, obtained from the Alabama Department of Public Health (ADPH) were analyzed for 67 Alabama counties. Associations between county characteristics and vaccine distribution were assessed using Pearson correlations and linear models.Population size, number of hospitals, and number of nursing homes per county correlated significantly with vaccine distribution (p< .0001). Population size consistently influenced vaccine distribution across quarters. County Social Vulnerability Index (SVI) showed no significant association with vaccine doses per quarter. Alabama’s vaccine distribution aligned with national priorities, emphasizing healthcare personnel and adults over the age of 65. SVI did not significantly affect vaccine distribution, indicating equitable distribution across socioeconomic groups.

Abstract: Background/objectives: Propolis (bee glue) is a complex biological substance produced by honeybee (Apis mellifera L.) and used as a natural remedy due to its therapeutic properties, including anti-inflammatory potential. The present research aimed to investigate the phenolic content, antioxidant, acetylcholinesterase inhibitory, antihemolytic activity and ex vivo anti-inflammatory activities of dimethylsulphoxide (DMSO) extracts of six propolis samples (P1-P6) from three regions of Bulgaria. Methods: the total phenolic content (TPC) and the total flavonoid content (TFC) were evaluated according to the standard methods; the antioxidant activity was assessed by the DPPH and FRAP assays; the anti-acetylcholinesterase activity was determined by the acetylcholinesterase inhibition assay; the antihemolytic activity was assessed by the degree of red blood cell (RBC) membrane stabilization; ex vivo anti-inflammatory activity was assessed by the expression of interleukin-1β (IL-1β) and nitric oxide synthase (NOS3) in smooth muscle preparations (SMPs) of a rat’s stomach. Results: The DMSO propolis extracts exhibited TPC from 189.30 to 290.80 mg GAE/g, TFC 64.41 to 151.60 mg QE/g and significant antioxidant activity (from 863.73 to 1799.22 mM TE/g determined by the DPPH assay, and from 796.86 to 1168.02 mM TE/g by the FRAP assay). The values of acetylcholinesterase inhibitory activity at concentration of 1 mg/mL ranged between 40.12 % and 46.44 %, with IC50 values between 1.07 and 1.39 mg/mL. All propolis extracts demonstrated high antihemolytic activity, which at concentration of 0.5 mg/mL showed protection of RBC between 76.28 and 89.32 %, with IC50 values varying from 0.06 to 0.14 mg/mL. The results of the immunohistochemical analysis showed that propolis extracts P1, P2, P3, P4 and P6 suppressed the expressions of IL-1β and NOS3 in varying degrees. The samples P1 and P2 completely suppressed NOS3 expression and strongly reduced the intensity of IL-1β expression; consequently, they had the highest ex vivo anti-inflammatory activity. Conclusions: Based on the results obtained, we can conclude that the investigated Bulgarian propolis samples possessed promising antioxidant capacity and anti-inflammatory potential. Therefore, they can find application as prospective therapeutic agents.

Abstract: With around 40 species spread throughout temperate and subtropical environments, mostly in East Asia and North America, the genus Lespedeza (L.) (Fabaceae) include Particularly in antioxidant, anti-inflammatory, anticancer, and antidiabetic uses, L. species show notable pharmacological promise due in great part to their high polyphenolic content. The polyphenolic profiles and bioactivities of L. capitata, L. cuneata, and L. bicolor are investigated in this work with an eye on extraction efficiency, total polyphenolic content (TPC), total flavonoid content (TFC), and antioxidant capacity. Corresponding with its higher DPPH radical scavenging IC50 (35.4 µg/mL) and ferric reducing antioxidant power (FRAP) of 912.3 µmol Fe²⁺/g, L. bicolor showed the greatest TPC (190.4 mg GAE/g) and TFC (109.2 mg QE/g). While L. bicolor exhibited strong neuroprotective and anticancer activity, L. cuneata showed strong α-glucosidase inhibition (IC50 = 28.1 µg/mL). L. capitata is nevertheless a great source of bioactive molecules even with its modest bioactivity. The results highlight the possibilities of L. species in nutraceutical and medicinal uses, therefore justifying further study on their bioavailability and molecular processes.

Abstract: During tissue injury or infection, leukocytes are activated to produce proinflammatory mediators, which trigger the immune system to produce anti-inflammatory and analgesic molecules. Our previous studies provide evidence that synthetic microneurotrophins, like BNN27, exert significant analgesic and anti-inflammatory effects during Complete Freund’s Adjuvant (CFA)-induced inflammation and pain. Thus, the aim of the present study was to examine if the effect of BNN27 on inflammatory pain is mediated at least in part by activation of T-lymphocytes. For this purpose, six hr following the injection of CFA, spleens were harvested in PBS, lymphocytes were collected and placed in medium containing concanavalin-A and IL-2 to prompt T-lymphocyte proliferation and differentiation. Cells were then treated with BNN27 at different concentrations and the media and cells were collected for ELISA and PCR assays. The proliferation rate of T-cells was also examined using the MTT assay. Our results showed that BNN27 significantly increased the proliferation of T-lymphocytes. In addition, BNN27 significantly decreased IL-6 and TNF-α protein levels, while it increased the mRNA expression of μ-opioid receptor and opioid peptides PENK and POMC at different time points. Our data demonstrate considerable anti-inflammatory and analgesic effects of BNN27, making it a promising molecule for inflammation and pain management.

Abstract: In this study, we developed a multifunctional graphene oxide (GO)-based nanoprobe co-loaded with antisense peptide nucleic acid (PNA) and the chemotherapeutic agent doxorubicin (DOX). The nanoplatform was strategically functionalized with folic acid ligands to enable folate receptor-mediated tumor targeting. Upon cellular internalization, the antisense PNA component selectively hybridized with human telomerase reverse transcriptase (hTERT) mRNA through sequence-specific recognition, inducing structural detachment from the GO surface. This displacement restored the fluorescence signal of previously quenched fluorophores conjugated to the PNA strand, thereby enabling real-time in situ detection and quantitative fluorescence imaging of intracellular hTERT mRNA dynamics. The antisense PNA component effectively suppressed hTERT mRNA expression and downregulated telomerase activity via an antisense gene regulation pathway, while pH-responsive release of DOX induced potent cancer cell apoptosis through chemotherapeutic action. This combinatorial therapeutic strategy demonstrated enhanced anticancer efficacy compared to single-modality treatments, achieving 60% apoptosis induction in HeLa cells through coordinated gene silencing and chemotherapy. The study establishes GO as a promising dual-drug nanocarrier platform for developing next-generation theranostic systems that integrate molecular diagnostics with multimodal cancer therapy.

Abstract: Neutrophil Extracellular Traps (NETs) play a crucial role in the pathophysiology of many debilitating conditions, including autoimmune diseases, inflammatory diseases, and cancer. As a result, NET-targeted therapies have been investigated in search of effective treatment strategies. Despite promising preclinical findings, clinical translation of NET inhibitors has had limited success. These preclinical studies have faced limitations such as mouse models that inaccurately reflect human disease dynamics, as well as the complexity of NETs regarding its diverse morphology and convoluted pathways to formation relative to pathology. The NET inhibitors themselves have several limitations, including off-target effects and bioavailability issues. The challenges facing NET-targeted therapies reported here may explain what is required to go from bench to bedside successfully.

Abstract: Cadherins are key cell adhesion molecules that engage in extracellular homophilic binding. CDH15/M‐cadherin is localized to the apical surface of muscle satellite cells (SCs), which play a critical role in tissue regeneration after injury. Although CDH15 is considered a marker of SCs, there is no anti-CDH15 mAb suitable for flow cytometry. We developed anti-CDH15 monoclonal antibodies using the Cell-Based Immunization and Screening (CBIS) method containing a flow cytometry-based high-throughput screening. In flow cytometry, a clone Ca15Mab-1 (IgG1, κ) reacted with human CDH15-overexpressed Chinese hamster ovary-K1 (CHO/CDH15) cells. Furthermore, Ca15Mab-1 recognizes endogenous CDH15-expressing human osteosarcoma (Saos-2) and mouse myoblast (C2C12) cell lines. The dissociation constant values of Ca15Mab-1 for CHO/CDH15, Saos-2, and C2C12 were determined as 6.9 × 10⁻10 M, 8.4 × 10⁻10 M, and 1.6 × 10⁻⁹ M, respectively. Furthermore, Ca15Mab-1 can detect endogenous CDH15 in immunoblotting and immunohistochemistry. Ca15Mab-1, established by the CBIS method, is versatile for basic research and is expected to contribute to clinical studies such as antibody therapy.

Abstract: Generative artificial intelligence (AI) has emerged as a disruptive paradigm in molecular science, enabling algorithmic navigation and construction of chemical and proteomic spaces through data-driven modeling. This review systematically delineates the theoretical underpinnings, algorithmic architectures, and translational applications of deep generative models—including variational autoencoders (VAEs), generative adversarial networks (GANs), autoregressive transformers, and score-based denoising diffusion probabilistic models (DDPMs)—in the rational design of bioactive small molecules and functional proteins. We examine the role of latent space learning, probabilistic manifold exploration, and reinforcement learning in inverse molecular design, focusing on optimization of pharmacologically relevant objectives such as ADMET profiles, synthetic accessibility, and target affinity. Furthermore, we survey advancements in graph-based molecular generative frameworks, LLM-guided protein sequence modeling, and diffusion-based structural prediction pipelines (e.g., RFdiffusion, FrameDiff), which have demonstrated state-of-the-art performance in de novo protein engineering and conformational sampling. Generative AI is also catalyzing a paradigm shift in structure-based drug discovery via AI-augmented molecular docking (e.g., DiffDock), end-to-end binding affinity prediction, and quantum chemistry-informed neural potentials. We explore the convergence of generative models with Bayesian retrosynthesis planners, self-supervised pretraining on ultra-large chemical corpora, and multimodal integration of omics-derived features for precision therapeutics. Finally, we discuss translational milestones wherein AI-designed ligands and proteins have progressed to preclinical and clinical validation, and speculate on the synthesis of generative AI, closed-loop automation, and quantum computing in future autonomous molecular design ecosystems.

Abstract: Erythropoietin-producing hepatocellular (Eph) receptor A3 (EphA3) is a member of the Eph receptor family, which binds to its respective ligands, ephrins. These interactions are essential for normal development and tissue homeostasis. Dysregulation of EphA3 has been reported to be associated with human hematopoietic malignancies, making it a promising target for therapy and diagnosis. Due to the high similarity of the extracellular domain among Eph receptors (more than 33% amino acid identity), generating highly specific monoclonal antibodies (mAbs) is crucial. We developed anti-human EphA3 mAbs in this study using the Cell-Based Immunization and Screening (CBIS) method. Among them, the clone Ea3Mab-20 (IgG1, kappa) exhibited high affinity and specificity in flow cytometry. The dissociation constant values of Ea3Mab-20 for CHO/EphA3 and Jurkat cells were determined to be 9.0 ± 0.3 × 10−9 M and 1.4 ± 0.1 × 10−9 M, respectively. Ea3Mab-20 showed no cross-reactivity with other Eph receptors in flow cytometry. Furthermore, Ea3Mab-20 demonstrated the suitability for detecting formalin-fixed paraffin-embedded cell samples in immunohistochemistry. Therefore, Ea3Mab-20 is valuable mAb for basic research and is expected to contribute to the clinical application of mAb for cancer therapy and diagnosis.

Abstract: Background/Objectives: Aminoglycosides (AG) have been extensively used to treat bacterial diseases for decades. Nevertheless, despite their effectiveness, several secondary adverse effects (auditory, renal, and neurological) have been evident. Although the mechanisms of these side effects of AG are still unclear, there is a consensus that megalin is a drug receptor that participates in AG endocytosis. We aimed to explore the interaction between megalin and AGs to explain their ototoxicity side effect by combining in silico studies and cell functionality assays. Methods: Molecular dynamics simulations on the 10^th CR domain of human megalin were performed using GROMACS. Seven commonly prescribed AG were docked against the surface of three conformations of this domain megalin derived from the simulations' trajectories. Gentamicin, the AG with the strongest affinity, was selected for cell functionality evaluation using HEK293 cells and Resazurin assays. Results: Docking results revealed that aspartic acids play a crucial role in the binding affinity to AGs, forming key electrostatic interactions. The models of the Megalin-AG complexes allowed the determination of electrostatic and non-electrostatic contributions to the free energy change of binding (ΔG_b). Gentamicin, Tobramycin, and Neomycin showed a higher affinity for megalin than Kanamycin, Hygromycin, Paromomycin, and Streptomycin. Cell functionality of HEK293 cells was reduced by Gentamicin. Conclusion: the 10^th CR domain of Megalin plays a critical role in AG-induced ototoxicity through electrostatic interactions mainly involving aspartic acid residues. It binds with higher affinity to Gentamicin, Tobramycin, and Neomycin than Kanamycin, Hygromycin, Paromomycin, and Streptomycin. Furthermore, we observed the reduced functionality of HEK293 cells induced by gentamicin. These results highlight megalin as a potential therapeutic target to mitigate/alleviate the adverse side effects of aminoglycoside.

Abstract: Background/Objectives: Sacituzumab govitecan (SG) is an antibody-drug conjugate targeting Trop-2, approved for use in metastatic triple-negative breast cancer (mTNBC) and more recently in hormone receptor-positive/HER2-negative (mHRPBC) subtypes. While clinical trials have demonstrated its efficacy, real-world da-ta—especially involving both molecular subtypes—remain scarce. This multicenter, retrospective study aimed to evaluate the real-life effectiveness, safety, and prognostic factors associated with SG treatment in patients with both mTNBC and mHRPBC. Methods: A total of 68 patients treated with SG between 2022 and 2025 were included from multiple oncology centers in Turkey. Patients with mTNBC were required to have received at least one prior chemotherapy line, while mHRPBC patients had received at least two prior chemotherapy lines in addition to hormone therapy. Clinical out-comes—including progression-free survival (PFS), overall survival (OS), and objective response rate (ORR)—were evaluated. Univariate and multivariate analyses were performed to identify factors influencing outcomes. Adverse events (AEs) were also documented and graded according to NCI-CTCAE v5.0. Results: The cohort included 35 (51.5%) mTNBC and 33 (48.5%) mHRPBC patients. The median PFS was 6.1 months, and the median OS was 12.5 months, with no significant differences between subtypes. The ORR was 52.9%, with a complete response observed in 10.3% of patients. Eastern cooperative oncology group performance status (ECOG PS) and liver metastasis were independent predictors of poorer PFS and OS. Prior immunotherapy did not negatively impact SG efficacy. SG was generally well tolerated; the most common AEs were alo-pecia, anemia, neutropenia, and diarrhea. Treatment discontinuation due to AEs was rare (2.9%). Conclusions: SG demonstrated comparable effectiveness and a managea-ble safety profile in real-world patients with both mTNBC and mHRPBC. Importantly, this study provides one of the first real-world datasets evaluating SG in the mHRPBC subgroup, highlighting its potential role beyond clinical trials. These results support SG as a valuable therapeutic option in heavily pretreated patients, warranting further prospective and biomarker-driven studies.

Abstract: Background: Community-acquired pneumonia (CAP) is a significant lower respiratory tract infection that poses challenges in treatment due to rising antimicrobial resistance (AMR). Rational antibiotic use is crucial for effective management and reducing the risk of resistant pathogens. This study aims to assess the rational use of antibiotics in treating CAP at Ndola Teaching Hospital (NTH) and evaluate adherence to established guidelines. By examining prescribing practices, the study seeks to identify gaps and inform best practices that enhance antibiotic stewardship. Ultimately, the findings will contribute to improving patient outcomes and guiding antibiotic prescriptions in similar healthcare settings in Zambia. Objective: To assess the rational use of antibiotics in the management of community acquired pneumonia at Ndola Teaching Hospital. Methodology: This was a mixed-method study that assessed the rational use of antibiotics in managing CAP at NTH. Data was collected and analysed using IBM SPSS Statistics version 26, employing Chi-square tests and logistic regression to identify factors influencing in-hospital mortality. Results: Out of 142 patient files reviewed, most patients were female (61.3%) and under 65 years old (69.0%), with ceftriaxone being the most prescribed antibiotic. Significant factors influencing in-hospital mortality included age over 65, length of hospital stay, allergies, co-morbidities, and management inconsistent with the 2020 national Standard Treatment Guidelines (p < 0.000). Multivariable logistic regression revealed that older age (aOR: 0.295, CI: 0.173-0.418, p < 0.000) and Length of hospital stay (aOR: 0.118, CI: 0.058-0.178, p < 0.000) significantly increased mortality risk. Additionally, 41.2% of prescribers had not seen the guidelines, highlighting the need for better dissemination and improved resources for effective CAP management at NTH. Conclusion: This study emphasized the importance of improved adherence to national treatment guidelines. The implementation of educational interventions and the promotion of collaboration among healthcare professionals are essential to optimizing antibiotic use in the management of CAP, which could lead to reduced mortality rates and improved patient outcomes.

Abstract: The development of new anticancer therapies remains challenging due to tumor heterogeneity and the frequent emergence of multidrug resistance (MDR). Natural products have garnered increasing attention as alternative or complementary therapeutic agents due to their bioactivity and reduced toxicity. Polyphenols, particularly curcumin and its derivatives, have shown potential in modulating signaling pathways, enhancing chemosensitivity, and overcoming drug resistance. In this study, we discovered the anticancer potential of Dimethoxycurcumin, a synthetic curcumin analog identified through consensus fingerprint similarity screening. Focusing on the ATP-binding cassette (ABC) transporter family—key mediators of drug efflux—we examined the impact of Dimethoxycurcumin on ABCC3 (MRP3), a transporter implicated in tumor cell survival and resistance. Our in vitro experiments demonstrated that Dimethoxycurcumin significantly reduced cell viability and colony formation, indicating a strong inhibitory effect on ABCC3 function. These results suggest that Dimethoxycurcumin may sensitize cancer cells to chemotherapy by targeting resistance pathways. This study supports the therapeutic value of plant-derived compounds and their derivatives in oncology and contributes to a better understanding of how functional antioxidants may interact with MDR-related transporters. Targeting ABC transporters with natural compound derivatives may offer a promising strategy for developing more effective and less toxic anticancer therapies.

Abstract: Neuron cell culture stands at the forefront of neuroscience innovation, offering unparalleled insights into neuronal development, pathology, and regeneration. This review critically examines advances and persistent obstacles in culturing neurons, with a focus on axon and dendrite growth—a pivotal yet underexplored frontier for regenerative medicine. We synthesize breakthroughs in extracellular matrix (ECM) engineering, 3D biomimetic microenvironments, and molecular interventions while highlighting intrinsic challenges such as limited neuronal longevity, tumorigenicity risks in stem cell approaches, and reproducibility gaps. Introducing a biomimetic engineering framework, we liken neuronal regeneration to a multidimensional optimization problem, where balancing mechanical, biochemical, and epigenetic variables dictates functional outcomes. Key findings include: 1. 3D hydrogels mimicking brain ECM enhance neurite outgrowth by 40–60% compared to 2D systems. 2. Secretory pathway disparities between axons and dendrites reveal evolutionarily conserved growth mechanisms. 3. Tumorigenicity remains a critical barrier, with CRISPR-Lin28-edited iPSCs reducing teratoma formation by 65% in preclinical models. We advocate for standardized, scalable protocols and CRISPR-epigenetic tools to silence inhibitory pathways (e.g., Nogo-A). By bridging in vitro models with clinical translation, this work charts a roadmap for overcoming regenerative bottlenecks in neurodegenerative diseases and CNS injuries.

Abstract: Microbial contamination in pharmaceutical products poses a significant threat to patient safety and drug efficacy. Despite stringent regulatory frameworks, discrepancies between the European Pharmacopoeia (Ph. Eur.) and the United States Pharmacopeia (USP) complicate standardization. This review examines microbiological contamination trends in pharmaceutical recalls from 2020 to 2024, identifies common contaminants, and evaluates rapid microbiological detection methods and alternative antimicrobial strategies. A cross-sectional study of all current recalls, market withdrawals, and safety alerts published by the European competent authorities pertaining to drugs was conducted. A manual review of all the recalls was also conducted to extract additional information including name of product and type, reason for contamination, and responsible contaminant. Contaminant prevalence, sterility compliance issues, and regulatory gaps were analyzed. Differences in microbiological testing methodologies between Ph. Eur. and USP were compared, alongside emerging rapid detection technologies such as Next-Generation Sequencing (NGS) and MALDI-TOF mass spectrometry. Data from recalls in Europe between January 2020 and December 2024 indicate that approximately 70% (N=62) of reported contamination cases lack specific microorganism identification, with Burkholderia cepacia and Ralstonia pickettii being the most frequently reported contaminants. Recalls of sterile pharmaceuticals, including infusion solutions and eye drops, increased significantly in 2023 and early 2024. While traditional sterility testing remains standard, novel technologies such as AI-assisted microbial identification and metagenomics offer promising alternatives for enhanced contamination control. Regulatory harmonization and improved transparency in contamination reporting are essential to mitigate pharmaceutical microbiological risks.

Abstract: The synthesis of silver nanoparticles (AgNPs), must be a controlled process in order to obtain nanoparticles of adequate morphology and size according to the purpose pursued. The aim of this study was to perform a synthesis of AgNPs and the complex formed with antibiotics clindamycin, that could be functionalized with dental materials to improve their drug-bond fungicidal and bactericidal. The synthesis of nanoparticles was achieved by forming a conjugate from a chemical reduction of silver nitrate (AgNO₃) with polyvinylpyrrolidone (PVP) as a reducing agent and used in medicine because it is an inert and environmentally friendly polymer, polyethylene glycol (PEG) was also used as a stabilizing agent, resulting in the formation of AgNPs with a diameter of less than 100 nm. The plasmon resonance of AgNPs was detected at a wavelength of 426 nm, and the AgNPs-clindamycin complex was detected at 443 nm. This was done in order to functionalize them with acrylic polymers for dental use, with the goal of generating a bactericidal and fungicidal effect with drugs such as clindamycin. The results obtained suggest that it may be possible to use nanospheres linked to clindamycin, based on its antimicrobial properties and characteristics in biomedicine.