2025年 · 第08卷第03期

Dear Editor,

Transdermal drug delivery offers the benefits of first-pass metabolism avoidance, high bioavailability, a low dose, and high patient compliance. Ethosomes are lipid-based vesicles containing phospholipids, ethanol, and water that enhance drug penetration by overcoming the barrier of the skin. Ethosomes can encapsulate lipophilic as well as hydrophilic drugs to increase their efficacy. Zingerone (ZNE) is a major component found in gingerroot and has potent antidiabetic, antioxidant, and antispasmodic activities. ZNE has low solubility in aqueous media, which leads to low oral bioavailability. ZNE-loaded ethosomes were prepared via the cold method. The ethosomes were optimized by a 3-level and 2-factor full factorial design. The independent variables selected were ethanol (%) and soy lecithin (%).The dependent variables selected were flux (μg/cm²/h) and entrapment efficiency (%). The optimized formulation was evaluated for size, polydispersity index, zeta potential, entrapment efficiency, in vitro drug release, and ex vivo skin drug permeation.The optimized formulation had an average vesicle size of 77.12 ± 1.89 nm, a polydispersity index of 0.350 ± 0.013, a zeta potential of -56.9 ± 1.25 mV, an entrapment efficiency of 75.83% ± 1.53%, in vitro drug release of 85.97% ± 1.92% (after 24 h), and ex vivo skin drug permeation of 78.52% ± 1.62%. The optimized formulation was converted to a gel formulation and characterized for in vitro parameters. The percent permeation of ZNE through rat skin (ex vivo) from the ethosomal gel was greater (73.12% ± 1.76%) than that from the conventional gel (38.17% ± 1.82%). This study reveals the substantial potential of ZNE-loaded ethosomes for transdermal delivery and for use in the management of systemic diseases.

This study aimed to investigate the impact of tertiary-lymphoid-structure-related genes on the clinical prognosis and tumor immune environment of patients with gastric cancer. Using The Cancer Genome Atlas data, 23 differentially expressed genes associated with the tumor microenvironment were identified and used to develop a prognostic model. Univariate and multivariate Cox regression analyses were conducted to assess the prognostic value of the model. The results revealed that high-risk patients presented increased activity in hypoxia, angiogenesis, epithelial–mesenchymal transition, and transforming-growth-factor-beta-signaling-related pathways, whereas low-risk patients presented increased activity in CD4+ T-cell-infiltration-related pathways. High-risk patients had lower survival rates and a worse response to immunotherapy. This model serves as an independent predictor of the survival of gastric cancer patients and can aid in immunotherapy decision-making.

The ocular delivery of drugs has always presented a pharmaceutical challenge. Various ocular barriers, such as reflex blinking, tear turnover, epithelial tight junctions, metabolism in ocular tissues, efflux pumps, nasolacrimal drainage, and other blood ocular barriers, restrict corneal permeation to ocular therapeutic moieties. This has limited the ocular bioavailability for many drugs. The short residence time of the drug on the ocular surface area also limits bioavailability. The small size and attractive surface properties of liposomal formulations offer advantages in ocular drug permeation. Accordingly, liposome-based preparations have attracted increasing attention from pharmaceutical researchers for delivering drugs on the ocular surface. Recent research has supported the potential of liposomal carriers for the successful delivery of various drugs, including antiglaucoma, anti-inflammatory, anti-infection, and anti-hypertensive drugs. The various ocular barriers are discussed here in detail, and the synthesis regimes of several liposomal drug carriers are described along with their applications in delivering different therapeutic agents to the ocular region. This review concisely describes the current status and future prospects of liposomal drug delivery systems for ocular drug delivery.

Alzheimer’s disease (AD) is a progressive neurodegenerative disorder characterized by cognitive decline and memory loss caused by the degeneration of neurons and the accumulation of amyloid plaques and tau tangles in the brain. The exact etiology of AD remains unclear, although both genetic and environmental factors play important roles. Key pathological features include synaptic dysfunction, oxidative stress, and neuroinflammation. Current treatments focus mainly on symptom relief through cholinesterase inhibitors and N-methyl-_D-aspartate receptor antagonists. However, there is an ongoing effort to discover disease-modifying therapies. Recent clinical trials are investigating innovative approaches such as amyloid-targeting agents, tau aggregation inhibitors, and gene therapies. This paper offers a thorough overview of AD, presenting its fundamental aspects, contributing factors, primary disease mechanisms, current therapeutic strategies, and a detailed examination of ongoing clinical trials. In the context of advancing research, this paper provides valuable insights into the multifaceted approaches being explored to improve the understanding and management of this challenging neurodegenerative disorder.

Antibiotic resistance is an unrelenting global health crisis. The overuse of antibiotics has led to the emergence of multidrug-resistant bacteria, making infections increasingly difficult to treat. To combat this, novel therapeutic approaches are urgently needed. Current strategies include antivirulence therapy, passive immunization, antimicrobial peptides, vaccines, phage therapy, and botanical and liposomal nanoparticles. These methods aim to reduce the pressure on antibiotics to mitigate the development of resistance. Future directions involve exploring combination therapies that combine antibiotics with biologics and nonantibiotic adjuvants. Intelligent delivery strategies and antimicrobial stewardship are also crucial for effective infection control. By integrating these approaches, we can combat antibiotic resistance and protect the natural microbiome. This article reviews these multifaceted strategies to highlight the ongoing battle against antibiotic resistance and how it can be better managed to ultimately preserve the effectiveness of antibiotics for future generations.

Virtual screening (VS) has become an essential computational tool in drug discovery that helps to identify bioactive compounds by predicting their interactions with biological targets. This approach, which includes both ligand-based and structure-based methods, aims to discriminate between active and inactive molecules to facilitate the identification of potential therapeutic agents. Despite important advances, challenges remain in accurately predicting ligand–receptor interactions, managing large chemical libraries, and increasing hit identification efficiency. These limitations, coupled with assumptions made by computational tools and data-driven errors, underscore the need for improved techniques to increase prediction precision and reduce false positives. This study employed advanced computational tools for VS, focusing primarily on molecular docking and ligand–protein interaction analysis.AutoDock, known for its Lamarckian genetic algorithm, was used for docking simulations, incorporating pharmacy grids to assess ligand-binding affinities. Additionally, CHARMM software was applied for molecular dynamics simulations to calculate empirical energy functions. AI-driven algorithms such as KarmaDock and DeepDock were utilized for large-scale ligand screening and for improving protein–ligand docking accuracy. Machine learning-based scoring systems and quantitative structure–activity relationship (QSAR) models improved binding affinity predictions.

The development of genomic sequencing technology, from conventional techniques to state-of-the-art inventions, has greatly improved our understanding of genetic material. This review examines important advancements in sequencing techniques and how they have revolutionized genomics research. High-throughput capabilities made possible by next-generation sequencing (NGS) have enabled quick and affordable genomic analysis. Digital gene expression profiling was made possible by methods such as serial analysis of gene expression (SAGE), whereas long-read capabilities without amplification were analyzed by single-molecule sequencing, as demonstrated by Oxford Nanopore’s nanopore-based sequencing and PacBio’s single-molecule real-time (SMRT) technology. Synthetic long-read sequencing is one example of a hybrid technique that enhances genome assembly. New techniques, such as epigenetic sequencing, have revealed that DNA alterations are essential for gene control, and spatial transcriptomics has connected gene expression to tissue-specific patterns. Target analysis and knowledge of microbial ecosystems were further enhanced via the use of sophisticated techniques, including metagenomics and CRISPR-Cas9-based sequencing. When combined, these techniques allow researchers to examine microbial communities, transcriptome diversity, genomic structure, and epigenetic changes with new clarity. For example, single-cell sequencing has shown molecular heterogeneity between cells, and long-read sequencing has revealed intricate isoform variants. Personalized medicine has advanced owing to spatial transcriptomics, which targets gene expression in specific organs. Digital sequencing has also improved the sensitivity of mutation identification, transforming the diagnosis of the disease. The convergence of sequencing technologies has ushered in a new era of genomic studies, opening the door to groundbreaking findings in ecology, biology, and medicine. Future developments will improve knowledge of human genetics by further improving sequencing accuracy, affordability, and applicability.

Chronic kidney disease (CKD) is a globally prevalent progressive disease characterized by complex interorgan signaling dysregulation. Fibroblast growth factor 23 (FGF23) and active vitamin D3 (VD3 and 1,25(OH)₂D₃) play critical roles in calcium–phosphate homeostasis. FGF23 reduces intestinal phosphate absorption by inhibiting 1,25(OH)₂D₃ synthesis, whereas 1,25(OH)₂D₃ negatively regulates FGF23 expression. In patients with CKD, this balance is disrupted, leading to elevated FGF23 levels, reduced 1,25(OH)₂D₃ levels, and exacerbated kidney dysfunction and complications. Since the primary source of VD3 is cutaneous synthesis via ultraviolet B radiation, sunlight exposure can markedly increase VD3 production, subsequently increasing 1,25(OH)₂D₃ levels. This suggests that sunlight therapy may serve as a potential intervention for modulating FGF23 and improving calcium–phosphate metabolism in patients with CKD. This review systematically summarizes the regulatory mechanisms of sunlight on VD3 synthesis, the role of FGF23 in CKD progression, and the potential applications of sunlight therapy in CKD management. Additionally, we discuss the applicability of sunlight therapy across different individuals, its limitations, and potential optimization strategies, providing insights for future research.