Rilei Jiang

Background.: Chemoresistance in triple-negative breast cancer (TNBC) remains a critical driver of relapse and metastasis. Current explanatory models—EMT reversibility, the absence of upstream CSC drivers, TGF-β pleiotropy, and fragmented RUNX2 functions—exist in isolation, lacking a unified framework. Main body: This review proposes the RUNX2-TGF-β positive feedback loop as a working hypothesis for a regulatory node that integrates these mechanisms. In this proposed circuit, TGF-β is postulated to activate RUNX2, which in turn amplifies TGF-β signaling, forming a self-reinforcing loop that is proposed to sustain CSC stemness, plasticity, metabolic adaptation, and drug tolerance. We synthesize the molecular evidence for this circuit, propose a candidate causal chain in chemoresistance, and critically evaluate cross-cancer evidence while distinguishing it from TNBC-specific findings. We then critically analyze why most targeted strategies succeed preclinically yet fail clinically, covering TGF-β inhibitor toxicity, RUNX2 “undruggability,” weak natural compound evidence, and the model-to-clinic gap. Conclusion: Given the limited direct causal evidence in TNBC, the RUNX2-TGF-β circuit is presented here as a working hypothesis rather than an established resistance mechanism. We propose a translational validation roadmap and highlight key unresolved questions. Unlike previous reviews, this work explicitly grades the evidence for each link in the circuit and designs a falsifiable experiment to test whether circuit disruption reverses established chemoresistance.

Background: Metabolic dysfunction-associated steatotic liver disease (MASLD) has emerged as a critical global health burden, driven by rising prevalence rates and earlier disease onset. Current therapeutic strategies remain limited to lifestyle interventions, with no approved pharmacotherapies targeting disease progression. Growing evidence highlights gut microbiota dysbiosis as a pivotal contributor to MASLD pathogenesis, characterized by disrupted intestinal barrier function, endotoxin translocation, and dysregulated bile acid (BA) and short-chain fatty acid (SCFA) metabolism. Preclinical studies suggest that specific botanical drugs and standardized polyherbal formulations may mitigate MASLD through microbiota modulation.Methods: A systematic review of preclinical and clinical studies (2015–2025) was conducted across PubMed, Web of Science, and CNKI. Search terms included “gut microbiota,” “Traditional Chinese Medicine (TCM),” and “MASLD,” focusing on studies with chemically defined botanical metabolites (purity >90%) or rigorously characterized polyherbal formulations. Exclusion criteria eliminated reports lacking microbial taxonomic validation (e.g., 16S rRNA sequencing), dose-response relationships, or mechanistic validation in animal models.Results: The synthesis of studies reveals that TCM ameliorates MASLD through three interconnected mechanisms: restoration of gut microbial diversity, reinforcement of intestinal barrier integrity via tight junction protein upregulation (e.g., ZO-1 and occludin), and normalization of BA/SCFA metabolism. Among the 10 botanical drugs and 11 formulations reviewed, significant reduction in liver steatosis were shown in rodent models. However, only 4% of these interventions progressed to human trials, and critical methodological inconsistencies were observed, including inconsistent phytochemical standardization and overreliance on homogeneous animal models (68% using male C57BL/6 mice).Conclusion: While TCM shows promise in modulating microbiota-liver crosstalk, clinical translation is hindered by insufficient phytochemical standardization, unvalidated multi-component synergies, and a paucity of human efficacy data. To bridge this gap, future research must prioritize randomized controlled trials with liver histology endpoints, ConPhyMP-guided quality control protocols, and humanized microbiota models. Rigorous validation of TCM’s microbiota-centric mechanisms—rather than empirical applications—will be essential to advance these interventions into clinically actionable therapies for MASLD.

Circular RNAs (circRNAs) and small non-coding RNAs of the head-to-junction circle in the construct play critical roles in gene regulation and are significantly associated with breast cancer (BC). Numerous circRNAs are potential cancer biomarkers that may be used for diagnosis and prognosis. Widespread expression of circRNAs is regarded as a feature of gene expression in highly diverged eukaryotes. Recent studies show that circRNAs have two main biological modulation models: sponging and RNA-binding. This review explained the biogenesis of circRNAs and assessed emerging findings on their sponge function and role as RNA-binding proteins (RBPs) to better understand how their interaction alters cellular function in BC. We focused on how sponges significantly affect the phenotype and progression of BC. We described how circRNAs exercise the translation functions in ribosomes. Furthermore, we reviewed recent studies on RBPs, and post-protein modifications influencing BC and provided a perspective on future research directions for treating BC.

Breast cancer (BC) has become the fifth most prevalent cause of cancer-related morbidity, attracting significant attention from researchers due to its heightened malignancy and drug resistance. Conventional chemotherapy approaches have proven inadequate in addressing all BC subtypes, highlighting the urgent need for novel therapeutic approaches or drugs. Curcumin (CUR), a phytochemical derived from Curcuma longa (turmeric), has shown substantial potential in inhibiting BC cell migration, metastasis, and proliferation. However, the use of CUR in this context comes with challenges due to its dynamic and easily degradable nature, poor aqueous solubility, low bioavailability, rapid metabolism, and swift systemic elimination, collectively limiting its clinical applications. As such, we provide an overview of the properties, synthesis, and characterization of the hybridization of CUR and its analogue with chemo-drug building blocks. We reviewed research from the last five years on CUR’s biogenesis with respect to the regulation of BC, revealing that CUR participates in arresting BC cells in the cell cycle and significantly induces apoptosis in BC cells. Information on the chemotherapeutic and antitumor mechanisms of CUR in BC, including regulation of the cell cycle, increased cell apoptosis, and inhibition of multidrug resistance (MDR), was compiled. Additionally, we provide an overview of CUR loaded into nanomaterials that are cotreated with other chemotherapeutic drugs, such as paclitaxel, thymoquinone, and tamoxifen. In this review, we discuss different types of nanoparticles that can be used for CUR delivery, such as polymeric nanoparticles, carbon nanotubes, and liposomes. By comparing the size, entrapment efficiency, drug-loading capacity, release time, biocompatibility, pharmaceutical scale, and reproducibility of various nanomaterials, we aimed to determine which formulations are better suited for loading CUR or its analogue. Ultimately, this review is expected to offer inspiring ideas, promising strategies, and potential pathways for developing advanced anti-BC strategy nanosystems in clinical practice.

Several studies have suggested the potential value of Houttuynia cordata as a therapeutic agent in lung cancer, but direct evidence is still lacking. The study aimed to determine the regulatory impact of a major H. cordata constituent derivative (sodium new houttuyfonate [SNH]) on lncRNA networks in non‐small cell lung cancer (NSCLC) to identify new potential therapeutic targets. After exposing NSCLC cells to SNH, we analysed the following: cell death (via flow cytometry, TUNEL and ASC speck formation assays), immune factors (via ELISA), gene transcription (via RT‐qPCR), subcellular localisation (via FISH), gene–gene and gene‐protein interactions (via dual‐luciferase reporter and RNA immunoprecipitation assays, respectively) and protein expression and distribution (via western blotting and immunocytochemistry or immunohistochemistry). In addition, statistical analysis (via one‐way ANOVA or unpaired t‐tests) was performed. Exposure to SNH promoted NSCLC cell pyroptosis, concomitant with significant up‐regulation of TCONS‐14036, a novel lncRNA. Mechanistic research demonstrated that TCONS‐14036 functions as a competing endogenous (ce)RNA by sequestering microRNA (miR)‐1228‐5p, thereby up‐regulating PRKCDBP‐encoding transcript levels. Indeed, PRKCDBP promoted pyroptosis by activating the NLRP3 inflammasome, resulting in CASP1, IL‐1β and GSDMD cleavage. Our findings elucidate the potential molecular mechanisms underlying the ability of SNH to suppress NSCLC growth through activation of pyroptosis via the TCONS‐14036/miR‐1228‐5p/PRKCDBP pathway. Thus, we identify a new potential therapeutic targets for NSCLC.