The Scutellaria baicalensis-Coptis chinensis herb pair ameliorates ulcerative colitis via integrated modulation of the aryl hydrocarbon receptor/NLRP3 inflammasome axis with tryptophan metabolites.

Therapeutic and toxicity targets for Euphorbia Kansui L. in treating hepatocellular carcinoma ascites revealed by ingredients pattern analysis accompanying vinegar processing.

Multiple mitochondrial stress dysregulation represents an emergent mechanism for inducing tumor cell death. While photodynamic (PDT) and cuproptosis therapies can generate oxidative and proteotoxic stress respectively, their cooperativity and effects are hampered by the uncontrolled spatiotemporal interaction with glutathione (GSH) overexpressed in the tumor microenvironment. Here, we developed a GSH-depleting nanodrug for synergistic mitochondria-targeting PDT and cuproptosis, by co-loading mitochondria-targeting photosensitizer PpIX-TPP with copper ionophore elesclomol (ES) into GSH-responsive dextran-based nanoassemblies. The interaction between GSH in tumor cells and disulfide bonds in nanodrugs led to GSH depletion, thereby triggering the responsive release of the loaded drugs and reducing the limitation of GSH on therapeutic effectiveness. The released PpIX-TPP effectively targeted mitochondria, inducing PDT effects under laser irradiation, causing oxidative stress and further reducing GSH levels. ES carried copper ions into tumor cells and selectively released them in mitochondria, inducing proteotoxic stress through cuproptosis and generating hydroxyl radicals via a Fenton-like reaction to cause extra oxidative stress. The orchestration of multiple mitochondrial stress pathways led to mitochondrial dysfunction, immunogenic cell death, and subsequent immune activation both in vitro and in vivo. This study provides a strategy for enhanced antitumor efficacy through mitochondrial stress amplification and immune activation. STATEMENT OF SIGNIFICANCE: Combining light-activated photodynamic therapy (PDT) with copper-dependent cell death (cuproptosis) is promising for treating melanoma. However, tumors often overexpress glutathione (GSH), which neutralizes reactive oxygen species generated by PDT and blocks the cancer-killing effects of copper, thus compromising both therapeutic modalities. Poor targeting further impairs the treatment effectiveness. Herein, we developed a smart drug delivery system that combines mitochondria-targeting PDT with elesclomol-induced cuproptosis to improve the precision of treatment while depleting GSH to eliminate its negative impact on the therapeutic effect. Our nanodrugs induce abnormal amplification of mitochondrial stress in cancer cells, triggering their self-destruction and activating the immune system to attack tumors. This work provides a new strategy to enhance melanoma treatment through mitochondrial stress amplification and immune activation.

Unveiling the RAAS-modulating terpenoid, Boerhadiffusene from Boerhavia diffusa L. and further envisage its potential anti-hypertensive activity through in silico and in vitro approaches.

Curcumol alleviates acute pancreatitis by inhibiting RIPK1/RIPK3/MLKL pathway-mediated necroptosis: integrated bioinformatics, network pharmacology, molecular docking and dynamics simulations, and experimental validation.

Mechanism of Inonotus hispidus in treating melasma: integrated in vivo, in vitro, network pharmacology and untargeted metabolomics investigation.

Danggui Buxue decoction ameliorates blood deficiency syndrome by suppressing IL-6/JAK2/STAT3 signaling pathway: An integrated Chinmedomics and bioinformatics study.

Yanxiao Di'naer decoction attenuates metabolic dysfunction-associated steatohepatitis through the regulation of gut microbiota and the metabolism of bile acid.

Targeting oral cancer with MicroRNA-based therapeutics: The role of tumor-suppressor miRNAs and exosome delivery.

From hands-on to family-on: Task-Shifting manual therapy techniques in post-stroke neuroplasticity - A retrospective comparative analysis of the Cogni-Famille protocol.

Identifying the active components and mechanisms of Toona sinensis pericarps for the treatment of diabetic kidney disease using network pharmacology and experimental verification.

Comparison of resectoscope and tissue removal device in managing chronic endometritis associated with endometrial polyps.

Modified Ganlu Xiaodu decoction attenuates airway barrier injury in Mycoplasma pneumoniae pneumonia by inhibiting ZBP1-mediated PANoptosis.

Systems pharmacology reveals the mechanism underlying gastrodiae rhizoma in improving stress-induced cognitive impairment: Protecting hippocampal synapses from excessive microglia-mediated pruning.

Multi-target mechanisms of Banxia Baizhu Tianma Decoction against MASH in a methionine-choline deficient mouse model: insights from a Multi-Omics Investigation.

Luteolin/polyvinyl alcohol/sodium alginate hydrogel enhances fibroblast-mediated tissue repair and facilitates pressure injury healing.

Research on the compatibility mechanism of the Tingli Dazao Xiefei Decoction by multi-organ metabolomics strategy.

Clinical depression is highly prevalent worldwide, yet many patients remain inadequately treated. Cognitive Bias Modification for Interpretation (CBMI) is a promising, cost-effective digital intervention that targets negative thinking patterns by repeatedly resolving ambiguous scenarios in neutral or positive ways. This study examined whether enhancing CBM-I for depression with graphics and character-based cognitive embodiment could improve presence, immersion, and therapeutic effects. A total of 138 participants were randomized into four groups: traditional CBM-I (Text-Only), enhanced CBM-I with pictures but no main character (No Character), enhanced CBM-I with pictures and character embodiment (Character), or Control. Procedures were identical across groups apart from the CBM-I version delivered. All three training groups significantly improved interpretation bias compared to Control, with no significant differences between training conditions. There were significant differences in the sense of presence but there were no significant differences in the sense of immersion among groups. Objective and subjective performance assessed by Anagram task showed no significant differences among groups. European participants exhibited significantly lower negative interpretation bias than non-European participants. The study lacked preregistration and may be underpowered for between-group comparisons. Visuals may not have been sufficiently realistic and some measures were not assessed at pre-post training. All active CBM-I conditions significantly reduced negative interpretation bias; however, no incremental benefit was detected for character-based cognitive embodiment or visual enhancements. Future studies should refine visual realism, adapt or develop cognitive embodiment measures, and utilize larger, preregistered samples to more rigorously evaluate the potential of character-based embodiment in CBM-I.

Jiangcaoxiang alleviates hepatic fibrosis through the Nrf2/GPX4 signaling pathway: Elucidated via integrated network pharmacology, multi-omics profiling, and experimental validation.

Preclinical validation of tetrahydroquinoline derivatives as EGFR inhibitor inducing glioblastoma cell death.