Deshi Dong

Peptides have emerged as pivotal agents in biomedicine due to their exceptional physicochemical properties, including high binding affinity, minimal immunogenicity, and precise target specificity. This review critically examines recent advancements in peptide-based strategies for pancreatic disorders, encompassing inflammatory conditions (e.g. pancreatitis), metabolic dysfunctions (e.g. diabetes), and notably, pancreatic cancer. We delineate the evolution of peptide therapeutics, emphasizing rational drug design approaches such as backbone cyclization and N-methylation to enhance metabolic stability, complemented by computational methodologies like molecular docking and AI-driven affinity maturation to optimize target engagement. The discussion highlights key innovations, including peptide probes for early diagnostic detection and peptide-drug conjugates for targeted intervention, while evaluating their efficacy in preclinical models and assessing their biosafety profiles. Furthermore, we survey current clinical trials aimed at translating these engineered peptides into clinical applications. Concluding with a perspective on precision medicine, we outline future trajectories necessitating advanced AI-integrated design frameworks and robust clinical validation to accelerate the bench-to-bedside translation of peptide technologies.

The review summarizes recent advances, challenges, and future perspectives in targeted drug delivery systems (DDSs) for pancreatic cancer (PC) therapy. Given the dismal prognosis of PC treatment is hindered by a dense desmoplastic stroma, profound hypoxia, limited T-cell infiltration, and abundant immunosuppressive myeloid populations, together forming physical and immunological barriers to effective therapy. Targeted DDSs based on organic, inorganic, and biological platforms (e.g., liposomes/lipid nanoparticles, polymeric nanoparticles, carrier-free drug self-assembly systems, hybrid inorganic–organic nanomaterials, and biomimetic carriers such as exosomes and protein nanocages) can enhance tumor accumulation and reduce off-target toxicity through active ligand–receptor targeting, microenvironment-adaptive delivery, and controlled release triggered by internal cues (pH, enzymes, reactive oxygen species, hypoxia) or external stimuli (light, heat, magnetic fields). Importantly, DDSs are designed to remodel the immunosuppressive tumor microenvironment (TME) by reprogramming tumor-associated macrophages, inhibiting myeloid-derived suppressor cells, activating innate immune sensing pathways, and overcoming stromal immune exclusion via stroma–immune co-modulation or transcytosis-enabled penetration. We further discuss precision-medicine opportunities, proposing biomarker-guided stratification and monitoring frameworks that link patient-specific TME features (e.g., stroma-high/immune-excluded, myeloid-dominant, weak innate priming) to rational DDS selection and combination regimens. Future development should prioritize clinically actionable combination strategies, localized/depot delivery when appropriate, and data-driven design and optimization (including artificial intelligence and machine learning) to accelerate personalized, translatable DDSs for improving pancreatic cancer outcomes.

Drug transporters and metabolizing enzymes are integral components of drug disposition, governing the absorption, distribution, metabolism, and excretion (ADME) of pharmaceuticals. Their activities critically determine therapeutic efficacy and toxicity profiles, particularly for antimicrobial agents, one of the most widely prescribed drug classes frequently co-administered with other medications. Emerging evidence highlights the clinical significance of the drug–drug interactions (DDIs) mediated by these systems, which may alter antimicrobial pharmacokinetics, compromise treatment outcomes, or precipitate adverse events. With the continuous introduction of novel antimicrobial agents into clinical practice, the role of drug transporters and metabolizing enzymes in the pharmacokinetics of antibiotics and the DDIs between antibiotics and other drugs mediated by these transporters and enzymes are important to determine in order to provide a theoretical basis for the safe and effective use of antimicrobial drugs in clinical use.

Background: Chronic pancreatitis (CP) is a fibro-inflammatory syndrome with unclear pathogenesis and futile therapy. CP’s microenvironment disrupts the fine-tuned balance of macrophage polarization toward a predominance of the M2-like phenotype associated with fibrosis. S100A9 is mainly expressed in monocytes as a potent regulator of macrophage phenotype and function. Here, we investigated the S100A9-related mechanisms underlying CP pathology induced by macrophages polarization.Methods: S100a9 knockout (S100a9_-/-) mice and an in vitro coculture system of macrophages overexpressing S100a9 and primary PSCs were constructed to investigate the effects and mechanisms of S100A9-mediated macrophage polarization on pancreatic inflammation and fibrosis underpinning CP pathology. Furthermore, a variety of S100A9-targeted small-molecule compounds were screened from U.S. Food and Drug Administration (FDA)-listed drug libraries through molecular docking and virtual screening techniques.Results: In CP progression, S100A9 upregulation induces M2 macrophage polarization to accelerate fibrosis via thousand-and-one amino acid kinase 3 (TAOK3)-c-Jun N-terminal kinase (JNK) signaling pathway, and loss of S100A9 reduces CP injury in vitro and in vivo. Coimmunoprecipitation (co-IP) and molecular docking experiments proved that S100A9 may interact directly with TAOK3 through salt bridges and hydrogen bonding interactions of the residues in the S100A9 protein. Furthermore, cobamamide and daptomycin, as inactivators of the S100A9-TAOK3 interaction, can improve CP by inhibiting the polarization of M2 macrophages.Conclusions: S100A9 is a significant promoter of M2-like macrophage-induced fibrosis in CP via the TAOK3-JNK signaling pathway. Cobamamide and daptomycin, targeted inhibitors of the S100A9-TAOK3 interaction, may become candidate drugs for CP immunotherapy.

Background: Ischemic stroke, a major cause of disability and the second leading cause of death, poses a significant public health challenge. Post‐stroke inflammation can harm the blood–brain barrier and worsen neurological deficits, which are key factors in neuronal damage in patients with ischemic stroke. Microglia are crucial in the central nervous system, involved in inflammation, neuronal damage, and repair after cerebral ischemia. While cellular immune metabolism has been widely studied, its role in ischamic stroke remains unclear. Aim: This review aims to examine how inflammation affects the phenotypic characteristics of immune cells after ischemic stroke and to explore the effects of the immune metabolic microenvironment on the phenotypic profiles and functions of microglia in ischemic stroke. Method: The review refers to the available literature in PubMed, searching for critical terms related to Ischemic stroke, neuroinflammation, microglia, and immunometabolism. Result: In this review, we found that during stroke progression, microglia can dynamically switch between pro‐inflammatory and anti‐inflammatory phenotypes. Microglial glycometabolism includes oxidative phosphorylation and glycolysis, and lipid metabolism involves lipid synthesis and breakdown. Modulating the production of inflammatory mediator precursors can induce an anti‐inflammatory phenotype in microglia. Conclusion: Thus, studying microglial metabolic pathways and their products may offer new insights for ischemic stroke treatment.

In the published article, there was an error. [There was a clerical error in writing].A correction has been made to [Abstract], [Findings], [Paragraph One]. This sentence previously stated:“[The PC strategies are considered more cost-effective than T-DXd when the WTP threshold is set at $36,058.06 per QALY.]”The corrected sentence appears below:“[The PC strategies are considered more cost-effective than T-DM1 when the WTP threshold is set at $36,058.06 per QALY.]”The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated.

Squamous cell carcinoma of the head and neck (HNSCC) is a difficult-to-treat cancer and treatment is challenging due to recurrence or metastasis. Therefore, there is an urgent need to explore more effective targeted therapies to improve the clinical outcomes and survival of HNSCC patients. The nanomedicine is emerging as a promising strategy to achieve maximal anti-tumor effect in cancer therapy. In this review, we summarize some important signaling pathways and present the current and potential roles of various nanomaterial drug-delivery formulations in HNSCC treatment, aiming to understand the pathogenesis of HNSCC and further improve the therapeutic efficacy of nanomaterial HNSCC. This article seeks to highlight the exciting potential of novel nanomaterials for targeted cancer therapy in HNSCC and thus provide motivation for further research in this field.