Gastrointestinal (GI) cancers are prevalent globally, with leading incidence and mortality rates among malignant tumors. Despite notable advancements in surgical resection, radiotherapy, and chemotherapy, the overall survival rates remain low. Hence, it is imperative to explore alternative approaches that enhance patient outcomes. Cluster of differentiation 47 (CD47), serving as an early diagnostic marker, is predominantly overexpressed in GI cancers and associated with poor prognosis. Targeting the CD47-signal regulatory protein alpha (SIRPα) signaling pathway may provide a novel strategy for GI cancers treatment. This study summarizes current knowledge of the structure and function of CD47 and SIRPα, their roles in signaling pathways, the prognostic significance of CD47, therapeutic strategies targeting the CD47-SIRPα signaling pathway in GI cancer, and highlights key issues for future investigations.

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Intrinsic gallium-68 labeling of nanoclays was developed with high labeling yield and radiostability that did good for their in vivo tracking.Image 1.

Natural antimicrobial peptides (AMPs) are promising candidates for the development of a new generation of antimicrobials to combat antibiotic-resistant pathogens. They have found extensive applications in the fields of medicine, food, and agriculture. However, efficiently screening AMPs from natural sources poses several challenges, including low efficiency and high antibiotic resistance. This review focuses on the action mechanisms of AMPs, both through membrane and non-membrane routes. We thoroughly examine various highly efficient AMP screening methods, including whole-bacterial adsorption binding, cell membrane chromatography (CMC), phospholipid membrane chromatography binding, membrane-mediated capillary electrophoresis (CE), colorimetric assays, thin layer chromatography (TLC), fluorescence-based screening, genetic sequencing-based analysis, computational mining of AMP databases, and virtual screening methods. Additionally, we discuss potential developmental applications for enhancing the efficiency of AMP discovery. This review provides a comprehensive framework for identifying AMPs within complex natural product systems.

Significant investment in nanocarrier drug delivery systems (Nano-DDSs) has yielded only a limited number of successfully marketed nanomedicines, highlighting a low rate of clinical translation. A primary contributing factor is the lack of foundational understanding of in vivo processes. Comprehensive knowledge of the pharmacokinetics of Nano-DDSs is essential for developing more efficacious nanomedicines and accurately evaluating their safety and associated risks. However, the complexity of Nano-DDSs has impeded thorough and systematic pharmacokinetic studies. Key components of pharmacokinetic investigations on Nano-DDSs include the analysis of the released drug, the encapsulated drug, and the nanomaterial, which present a higher level of complexity compared to traditional small-molecule drugs. Establishing an appropriate approach for monitoring the pharmacokinetics of Nano-DDSs is crucial for facilitating the clinical translation of nanomedicines. This review provides an overview of advanced bioanalytical methodologies employed in studying the pharmacokinetics of anticancer organic Nano-DDSs over the past five years. We hope that this review will enhance the understanding of the pharmacokinetics of Nano-DDSs and support the advancement of nanomedicines.

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Fluvoxamine (FXM) is a well-known selective serotonin reuptake inhibitor (SSRI) for treating depression and has recently been repurposed for efficacious treatment of coronavirus disease 2019. Although cyclodextrin (CD) encapsulation effectively improves the physicochemical properties of structurally diverse SSRIs, the molecular understanding of their associations is deficient. This comprehensive study used single-crystal X-ray diffraction integrated with density functional theory (DFT) calculation to provide deep insights into the conformationally flexible FXM and its inclusion complexation with β-CD. X-ray analysis revealed the first crystallographic evidence of the uncomplexed 3FXM-H⁺·3maleate^- (1). Three FXM-H⁺ ions are counter-balanced by three planar maleate^- ions to form a thin layer stabilized by infinite fused H-bond rings R₄ ⁴(12) and R₆ ⁴(16) and the interplay of π⋯π, CF⋯π and F⋯F interactions. For 2β-CD·2FXM-H⁺·maleate^2-·23·2H₂O (2), the tail-to-tail β-CD dimer encapsulates two FXM-H⁺ 4-(trifluoromethyl)phenyl moieties, which are charge-balanced by the rare non-planar maleate^2- and stabilized by N/OH⋯O H-bonds and F⋯F interactions. This is a host-guest recognition pattern uniquely observed for all β-CD complexes with halogen (X)-bearing SSRIs, indicating the essence of X⋯X interactions and the shielding of X-containing moieties in the wall of the β-CD dimer. DFT calculations unveiled that the monomeric and dimeric β-CD-FXM complexes and FXM isomers are energetically stable, which alleviates the numbness and bitterness of the orally administered drug as previously patented. Additionally, an insightful conformational analysis of FXM emphasizes the importance of drug structural adaptation in pharmacological functions.

Protozoan infections (e.g., malaria, trypanosomiasis, and toxoplasmosis) pose a considerable global burden on public health and socioeconomic problems, leading to high rates of morbidity and mortality. Due to the limited arsenal of effective drugs for these diseases, which are associated with devastating side effects and escalating drug resistance, there is an urgent need for innovative antiprotozoal drugs. The emergence of drug repurposing offers a low-cost approach to discovering new therapies for protozoan diseases. In this review, we summarize recent advances in drug repurposing for various human protozoan diseases and explore cost-effective strategies to identify viable new treatments. We highlight the cross-applicability of repurposed drugs across diverse diseases and harness common chemical motifs to provide new insights into drug design, facilitating the discovery of new antiprotozoal drugs. Challenges and opportunities in the field are discussed, delineating novel directions for ongoing and future research.

Quantitative structure-retention relationship (QSRR) is an important tool in chromatography. QSRR examines the correlation between molecular structures and their retention behaviors during chromatographic separation. This approach involves developing models for predicting the retention time (RT) of analytes, thereby accelerating method development and facilitating compound identification. In addition, QSRR can be used to study compound retention mechanisms and support drug screening efforts. This review provides a comprehensive analysis of QSRR workflows and applications, with a special focus on the role of artificial intelligence-an area not thoroughly explored in previous reviews. Moreover, we discuss current limitations in RT prediction and propose promising solutions. Overall, this review offers a fresh perspective on future QSRR research, encouraging the development of innovative strategies that enable the diverse applications of QSRR models in chromatographic analysis.

The NOD-like receptor protein 3 (NLRP3) inflammasome is essential in innate immune-mediated inflammation, with its overactivation implicated in various autoinflammatory, metabolic, and neurodegenerative diseases. Pharmacological inhibition of NLRP3 offers a promising treatment strategy for inflammatory conditions, although no medications targeting the NLRP3 inflammasome are currently available. This study demonstrates that clioquinol (CQ), a clinical drug with chelating properties, effectively inhibits NLRP3 activation, resulting in reduced cytokine secretion and cell pyroptosis in both human and mouse macrophages, with a half maximal inhibitory concentration (IC₅₀) of 0.478 μM. Additionally, CQ mitigates experimental acute peritonitis, gouty arthritis, sepsis, and colitis by lowering serum levels of interleukin-1β (IL-1β), IL-6, and tumor necrosis factor-α (TNF-α). Mechanistically, CQ covalently binds to Arginine 335 (R335) in the NACHT domain, inhibiting NLRP3 inflammasome assembly and blocking the interaction between NLRP3 and its component protein. Collectively, this study identifies CQ as an effective natural NLRP3 inhibitor and a potential therapeutic agent for NLRP3-driven diseases.