Acta Pharmaceutica Sinica B

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Neuroimmune circuit mediates apathy in cancer cachexia

Acta Pharmaceutica Sinica B. 2025, 15(12): 6731-6734.
Standardization of nasal airway structure model of Chinese Han nationality for characterization of nasal formulation spatial deposition atlases

Acta Pharmaceutica Sinica B. 2025, 15(12): 6698-6713.

The deposition characteristics of nasal formulations directly determine the efficacy of the drugs, whilst the complexity of human nasal airway structure encumbers quantitative evaluation of nasal spatial deposition. Male and female standard nasal airway structure models were calculated from computed tomography data of 128 Chinese Han nationality using statistical shape model. The deposition evaluation devices were further designed, and an imaging method was then employed to obtain drug deposition information. Furthermore, drug spatial deposition atlases were proposed by UV unwrapping, a mathematical mapping procedure flattening three-dimensional (3D) information to two-dimension bidirectionally, to achieve quantification of drug deposition fractions in the regions of interest. Moreover, the feasibility and universality of this method were verified by correlating it with the chemical quantitative results and computational fluid dynamic simulation of drug deposition of mometasone furoate nasal spray and hydroxypropyl methylcellulose nasal powder, respectively. Finally, the unique drug spatial deposition atlases of these two formulations in the male and female evaluation devices were generated, respectively. In summary, the standard nasal airway structure models of the Chinese Han nationality and the drug spatial deposition atlases provide scientific tools for the formulation optimization and quality control of nasal formulations.
CELMoD-antibody conjugates unlock a CD38 feedback loop in multiple myeloma

Acta Pharmaceutica Sinica B. 2025, 15(12): 6739-6740.
RDYH58 functional exosomes targeting myofibroblasts loaded with siFKBP10 for inhibition of collagen biosynthesis and secretion of IPF

Acta Pharmaceutica Sinica B. 2025, 15(12): 6681-6697.

Idiopathic pulmonary fibrosis (IPF) is a complex interstitial lung disease in which myofibroblasts are the primary effector cells. FK506-binding protein (FKBP10), a procollagen chaperone, is upregulated in IPF and primarily localizes to myofibroblasts. Exosomes have garnered significant attention as novel drug delivery vehicles, particularly when engineered. However, myofibroblasts remain underexplored in terms of engineered exosome-based therapies and associated drug targets. In this study, RDYH58, a peptide that targets myofibroblasts, was conjugated to the exosomal membrane protein Lamp2b to produce RDYH58-linked exosomes (RDYH58-exo). In vitro and in vivo experiments demonstrated that compared to unmodified exosomes (unm-exo), RDYH58-exo preferentially localized to myofibroblasts. A small interfering RNA targeting FKBP10 (siFKBP10) was loaded into exosomes using ultrasonic microfluidics method, and the antifibrotic effects of RDYH58-exo carrying siFKBP10 (RDYH58-siFKBP10) were assessed both in vitro and in vivo. The results demonstrated that RDYH58-siFKBP10 effectively silenced FKBP10 gene expression, significantly inhibiting fibroblast activation and extracellular matrix deposition, with superior antifibrotic efficacy compared to unmodified exosome vectors (unm-siFKBP10). RNA-seq analysis confirmed the pivotal regulatory role of FKBP10, providing critical evidence for the development of targeted therapeutic strategies. The RDYH58-siFKBP10 delivery system developed in this study demonstrates remarkable clinical translation potential.
LSD1 inhibition sensitizes anti-PD1 blockade immunotherapy by inhibiting the long-range attack of tumor-derived extracellular vesicles

Acta Pharmaceutica Sinica B. 2025, 15(12): 6657-6680.

Programmed cell death protein-1/programmed cell death ligand-1 (PD1/PD-L1) blockade has shown promise in cancer therapy but remains limited by low response rates. Recent efforts have explored strategies to enhance immunotherapy efficacy. Histone lysine-specific demethylase 1 (LSD1) inhibition can enhance tumor immune responses by downregulating PD-L1 expression. Furthermore, PD-L1 in tumor cell-derived extracellular vesicles (EVs) contributes to the immunosuppressive tumor microenvironment (TME) and promotes immune evasion. Here, we found that LSD1 inhibition can mediate the rearrangement of PD-L1 on tumor cell surfaces, reduce the secretion of EVs and PD-L1 levels in the TME, and ultimately block the long-range immunosuppression caused by tumor cell-released EVs. Therefore, we developed a TME-targeted synergistic therapy system with a dual mechanism in which anti-PD1 therapy blocks immune checkpoints, and forsythiaside A (FA) acts as an LSD1 inhibitor to regulate EVs secretion. Additionally, CD4⁺ T cells can directly kill tumor cells by inducing G1/S cell cycle arrest. Ultimately, this system activates the tumor immune response within the TME, effectively inhibiting the growth of non-small cell lung cancer tumors. Our work highlights the signaling role of EVs and the capacity of CD4⁺ T cells to arrest the cell cycle, offering a new approach to enhance response to anti-PD1/PD-L1 therapy.
Antisense molecules: A promising new therapy for atopic dermatitis

Acta Pharmaceutica Sinica B. 2025, 15(11): 5493-5514.

Atopic dermatitis (AD) is a common chronic inflammatory skin disorder affecting all age groups, especially children, with a prevalence of up to 20% globally. AD remains burdensome and incurable with current therapeutic strategies—ranging from trigger avoidance and skincare to medication—primarily address symptoms rather than disease modification, underscoring the imperative for innovative therapeutic paradigms. RNA-targeted therapies, particularly antisense molecules, have emerged as a transformative approach in precision medicine, with proven clinical success in diseases such as spinal muscular atrophy and familial chylomicronemia syndrome. These therapeutics achieve post-transcriptional regulation unattainable by conventional therapies, enabling direct targeting of messenger RNA (mRNA) and regulatory non-coding RNAs (ncRNAs) implicated in disease pathogenesis. Furthermore, skin is better suited to the antisense modulation due to the relatively easy access to target cells. Numerous studies have explored antisense-based targeting of key drivers in AD progression, yielding promising proof-of-concept results and prompting several early-stage clinical trials. This modality represents a paradigm shift in AD management—one that aligns with the broader revolution in RNA therapeutics reshaping modern medicine. This review critically examines the evolving role of antisense technology in AD, addressing both its mechanistic rationale and the translational challenges that must be overcome to realize its full clinical potential.
Intestinal barrier in chronic gut and liver diseases: Pathogenesis and therapeutic targets

Acta Pharmaceutica Sinica B. 2025, 15(11): 5515-5536.

The intestinal barrier is the primary defense that separates the host from the external environment, possessing several crucial physiological functions, including nutrient digestion, absorption, and protection against potentially harmful dietary antigens and pathogenic microorganisms. Nevertheless, various factors, such as diet, medications, circadian rhythm disturbances, gut microbiota, microbial metabolites, and genetic predisposition, can disrupt the intestinal barrier. Such disruption may lead to bacterial translocation, subsequently triggering enterohepatic and systemic inflammation. Impaired intestinal barrier has been implicated in the pathogenesis of numerous diseases, particularly chronic gut and liver diseases. In this review, we will summarize the fundamental functions of intestinal barrier and discuss clinical correlations between intestinal barrier dysfunction and diseases such as colitis, colorectal cancer, and chronic liver diseases including metabolic dysfunction-associated steatohepatitis, alcohol-associated liver disease, and primary sclerosing cholangitis. Additionally, we will also highlight some potential therapeutic strategies aimed at restoring barrier integrity to improve disease management.
Targeting pattern recognition receptors for cancer therapy: Mechanisms and strategies

Acta Pharmaceutica Sinica B. 2025, 15(11): 5537-5600.

Pattern recognition receptors (PRRs) play a crucial role in immune responses, acting as primary sensors for microbial and host-derived signals. PRRs, which include Toll-like receptors (TLRs), retinoic acid-inducible gene 1-like receptors, nucleotide-binding oligomerization domain-like receptors, C-type lectin receptors, and various cytoplasmic DNA sensors, are essential for initiating immune responses that regulate both inflammation and tumor immunity. Recent studies have highlighted their dual roles in cancer, where they can either suppress or promote tumor progression by influencing the tumor microenvironment and modulating responses to immunotherapy. In the context of cancer, PRRs not only activate immune cells but also contribute to immune evasion mechanisms within tumors. Therapeutically, targeting PRRs represents a promising approach for cancer treatment, with related drugs showing potential to enhance the efficacy of existing immunotherapies. Numerous PRR-based agents, particularly TLR agonists, are currently under clinical investigation for their ability to augment antitumor immunity and overcome resistance to immune checkpoint inhibitors. This review examines the molecular mechanisms by which PRRs influence cancer, with a focus on recent advancements in PRR-targeted therapies and their integration with contemporary immunotherapeutic strategies.
The epigenetic landscape of rheumatoid arthritis: Pathogenesis and drug therapeutic potentials

Acta Pharmaceutica Sinica B. 2025, 15(11): 5601-5631.

Rheumatoid arthritis (RA) represents a persistent autoimmune condition distinguished by a multifaceted etiology that encompasses both genetic and environmental factors. Recent progress in understanding the mechanisms behind RA pathogenesis has delved into the critical role of epigenetic regulatory processes, including DNA methylation, histone modifications, and the regulation by microRNAs (miRNAs). These findings provide new insights into the intricate nature of RA and pave the way for innovative therapeutic strategies. This review consolidates the latest developments in the epigenetic regulation of RA, concentrating on how these mechanisms affect the dysregulated signaling pathways associated with the disease. We analyze the roles of specific proteins that function as ‘writers’, ‘erasers’, and ‘readers’ in epigenetic modifications, highlighting their potential as targets for therapeutic intervention. Additionally, in view of the significance of miRNAs in the pathogenesis of RA, we deliberate on their involvement in disease progression and explore miRNA-based treatment strategies. By integrating these diverse epigenetic dimensions, this review offers a comprehensive epigenetic perspective on RA pathogenesis and identifies promising avenues for future research and therapeutic interventions.
Next-generation clinically relevant antibody detection: Unlocking electrochemical biosensors for critical disease management

Zheng Zhao, Zhiwei Chen, Jacques Crommen, Shengfeng Huang, Qiqin Wang, Zhengjin Jiang

Acta Pharmaceutica Sinica B. 2025, 15(11): 5632-5662.

Autoimmune diseases, cancers, and viral infections pose significant global health threats, characterized by chronic pathology, unregulated cellular proliferation, and rapid transmission, respectively, requiring urgent early warning and treatment strategies. Antibodies, primarily classified into autoantibodies and therapeutic antibodies based on their clinical roles, provide essential information and show considerable value in the precise diagnosis and treatment of these serious diseases. Among the technologies utilized in bioanalysis, electrochemical biosensors, with their unique advantages of rapid response, high sensitivity, miniaturization, cost-effectiveness and user-friendly operation, have been developed as a trending technology for precise diagnostic and therapeutic drug monitoring. This review systematically summarizes the relationships and roles of clinically relevant antibodies in autoimmune diseases, cancers, and viral infections, while detailing the composition, strategies, development, and application trends of relevant electrochemical biosensors. Furthermore, it highlights the remaining challenges and opportunities for the advancement and prospects of electrochemical sensors in the context of clinically relevant antibodies.

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