The heightened expression of lysine-specific demethylase 1 (LSD1/KDM1A) in multiple malignancies facilitates immune evasion, aiding in tumor survival; however, its role in shaping the gastric cancer (GC) tumor immune microenvironment remains incompletely defined. Here, we show that loss of tumor cell-intrinsic LSD1 skews M0 macrophage polarization into an anti-tumor M1 phenotype, enhances CD8⁺ T-cell recruitment and activation, and attenuates CD8⁺ T-cell exhaustion by suppressing M0 macrophage polarization into the pro-tumor M2 phenotype. Guided by these insights, we designed a quinoline-based reversible inhibitor series. Lead compound KL-1 suppresses LSD1 (IC50 = 18 nM) and reprograms macrophage–T-cell crosstalk in vivo. In a syngeneic GC model, KL-1 elicits robust tumor growth inhibition accompanied by increased intratumoral M1 macrophages and functional CD8⁺ T cells; depletion of either macrophages or CD8⁺ T cells abrogate the efficacy, establishing their necessity for response. These findings position LSD1 as a tractable epigenetic node for immune reprogramming in GC and identify KL-1 as a promising clinical candidate.

Inflammatory bowel disease involves chronic inflammation of the intestine and disruption of normal immune balance, often linked to gut microbiota dysbiosis. The beneficial bacterium Akkermansia muciniphila (A.muciniphila) is known to support intestinal health and immune regulation, but its specific effects on T cell responses remain unclear. Here, we present a comprehensive multi-omics dataset integrating RNA sequencing and quantitative proteomics analyses of splenic CD4⁺ T cells derived from wild-type C57BL/6 J mice subjected to dextran sulfate sodium elicited colitis, in the presence or absence of A.muciniphila supplementation. The dataset includes transcriptomic profiles, protein abundance quantification, and quality control metrics for reproducibility. These data provide a valuable resource for exploring how A.muciniphila modulates immune metabolism, signaling, and inflammatory pathways in CD4⁺ T cells during intestinal inflammation, supporting future multi-omics integration and comparative analyses of host–microbe interactions in IBD models.

Lysine-specific demethylase 1 (LSD1), the first identified histone lysine-specific demethylase, plays a crucial role in mediating immune responses in gastric cancer. Most LSD1 inhibitors undergoing clinical trials are irreversible, which has driven significant interest in developing structurally diverse reversible inhibitors. In this study, we present a potent 1,3,5-triazine-based LSD1 inhibitor, XP-2, discovered through high-throughput screening (HTS) of our in-house compound library and subsequent structure-activity relationship (SAR) studies, exhibiting a half maximal inhibitory concentration (IC50) of 0.116 μmol/L. XP-2 enhanced the susceptibility of gastric cancer cells to T cell-mediated cytotoxicity by downregulating programmed cell death ligand 1 (PD-L1) expression, thereby disrupting the programmed cell death protein 1 (PD-1)/PD-L1 interaction. Furthermore, XP-2 significantly inhibited the proliferation of gastric cancer cells without inducing notable toxicity. Pharmacokinetic evaluation revealed favorable oral exposure and a moderate half-life in mice. In conclusion, this study provided a promising LSD1 inhibitor with a novel scaffold and promising pharmacokinetic properties, supporting its further development as an immunomodulator for gastric cancer treatment.

Multidrug resistance (MDR) remains a formidable barrier to successful cancer treatment, driven by mechanisms such as efflux pump overexpression, enhanced DNA repair, evasion of apoptosis and the protective characteristics of the tumour microenvironment. Nanoparticle-based delivery systems have emerged as promising platforms capable of addressing these challenges by enhancing intracellular drug accumulation, enabling targeted delivery and facilitating stimuli-responsive and controlled release. This review provides a comprehensive overview of the molecular and cellular mechanisms underlying MDR and critically examines recent advances in nanoparticle strategies developed to overcome it. Various nanoparticle designs are analysed in terms of their structural and functional features, including surface modifications, active targeting ligands and responsiveness to tumour-specific cues. Particular emphasis is placed on the co-delivery of chemotherapeutic agents with gene regulators, such as siRNA, and the use of nanoparticles to deliver CRISPR/Cas9 gene editing tools as a means of re-sensitising resistant cancer cells. While significant progress has been made in preclinical settings, challenges such as tumour heterogeneity, limited clinical translation and immune clearance remain. Future directions include the integration of precision nanomedicine, scalable manufacturing and non-viral genome editing platforms. Collectively, nanoparticle-based drug delivery systems offer a multifaceted approach to combat MDR and hold great promise for improving therapeutic outcomes in resistant cancers.

Head and neck squamous cell carcinoma (HNSCC) is the sixth most common malignancy worldwide, with oral squamous cell carcinoma (OSCC) accounting for a significant portion of cases. Despite advancements in treatment, only modest gains have been made in HNSCC/OSCC control. Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) have emerged as targeted therapies for OSCC in clinical trials. However, their clinical efficacy remains a challenge. Cannabidiol (CBD), a non-psychoactive phytochemical from cannabis, has demonstrated anticancer and immunomodulatory properties. CBD induces apoptosis and autophagy and modulates signaling pathways often dysregulated in HNSCC. This review summarizes the molecular mechanisms of EGFR-TKIs and CBD and their clinical insights and further discusses potential implications of combination targeted therapies.

Kunzea ericoides (kanuka), a native plant of New Zealand, has a significant role in traditional medicine due to the presence of essential oils. Apart from these oils, this plant also is a source of many bioactive compounds, majority of which are polyphenols. However, there is lack of sufficient data supporting the extraction of polyphenols from kanuka plant leaves and investigating its bioactivity and phytochemical properties. The study aims to extract polyphenols from kanuka plant leaves with a conventional solvent-based method and determine the phytochemical analysis as well as bioactive potential. Extraction was performed with methanol and acetone as solvents. Polyphenolic prolife was analyzed with LC-MS. Bioactive analysis of kanuka leaf extract was carried out to determine total phenolic content and antioxidant activity. We investigated the cytotoxic effect of kanuka leaf extract on two triple-negative breast cancer cells—MDA-MB-231 and BT-549. LC-MS analysis confirmed kanuka leaf extract is a source of many polyphenols, some giving very prominent signals on TIC scan. Ten polyphenolic compounds were confirmed to be present in kanuka leaf extract based on MRM analysis. FRAP-CUPRAC analysis indicated significant antioxidant activity in the kanuka leaf extract. Antiproliferative analysis has confirmed cytotoxicity of the kanuka leaf extract on the triple-negative breast cancer cell lines. This study indicates that Kunzea ericoides leaf extract, rich in polyphenols, shows promising antioxidant and antiproliferative potential, warranting further investigation for therapeutic applications.

CDK4/6 inhibition represents a new generation of cancer therapies, targeting CDK4/6 complexes to induce cell cycle arrest in the G1 phase. These inhibitors have been widely used in combination with hormone receptor antagonists for treating ER+/HER2− breast cancer, achieving significant clinical success. Building on this progress, ongoing research explores novel combination therapies and expands the application of CDK4/6 inhibitors to other diseases. However, challenges remain, including variable cellular responses and the rapid development of drug resistance. Recent studies have uncovered new resistance mechanisms and their unexpected effects on cell metabolism, autophagy, and the tumor microenvironment beyond cell cycle arrest. This review provides a comprehensive overview of the mechanisms by which CDK4/6 inhibitors combat cancer and explores their potential for more effective and personalized treatment strategies.

Sperm-associated antigen 5 (SPAG5), also known as Astrin, was previously demonstrated as a biomarker for cellular resistance to major breast cancer therapies, including chemo-, endocrine- and targeted therapy. However, the contribution of SPAG5 to anthracycline- and taxane-based chemotherapy in triple-negative breast cancer (TNBC) remains controversial. In the present study, the SPAG5 knockout cell model was established by using clustered regularly interspaced palindromic repeats (CRISPR)-CRISPR-associated protein 9 (Cas9) system in MDA-MB-231 and BT549 TNBC cell lines. The knockout of SPAG5 was confirmed on both gene and protein levels using genomic PCR, DNA sequencing and western blotting. The functional loss of SPAG5 was determined by colony-formation assay. SPAG5-regulated doxorubicin- and docetaxel-resistance was assessed by MTT and apoptosis assays. The results indicated that all the SPAG5 knockout MDA-MB-231 and BT549 clones were biallelic, where one allele was replaced by the donor template, and the other allele had the same “T” insertion (indel) adjacent to the cutting sites of gRNAs at the exon 1 boundary, irrespective of the gRNAs and cell lines. The locus of indel interrupted the SPAG5 transcription by damaging the GT-AG mRNA processing rule. Deletion of SPAG5 decreased clonogenicity in both MDA-MB-231 and BT549 cells. SPAG5 was able to regulate the resistance and the drug-induced apoptosis of both doxorubicin and docetaxel. In conclusion, recombinant plasmid-based CRISPR-Cas9 technology can be used to delete the SPAG5 gene in the TNBC cell lines. SPAG5 has an important role in regulating cell proliferation and doxorubicin- and docetaxel-resistance in MDA-MB-231 and BT549 cells.

Gemcitabine-based chemotherapy has been widely adopted as the standard and preferred chemotherapy regimen for treating advanced pancreatic cancer. However, the contribution of multidrug resistance protein 5 (MRP5) to gemcitabine resistance and pancreatic cancer progression remains controversial. In the present study, the effect of silencing MRP5 on gemcitabine resistance and cell proliferation and migration of human pancreatic cancer MIA Paca-2 and PANC-1 cells was investigated by using short-hairpin RNA delivered by lentiviral vector transduction. The knockdown of MRP5 was confirmed on both mRNA and protein levels using qPCR and surface staining assays, respectively. MRP5-regulated gemcitabine sensitivity was assessed by MTT, PrestoBlue and apoptosis assays. The effect of MRP5 on pancreatic cancer cell proliferation and migration was determined using colony-formation, wound-healing and Transwell migration assays. The interaction of gemcitabine and cyclic guanosine monophosphate (cGMP) with MRP5 protein was explored using molecular docking. The results indicated that the MRP5 mRNA and protein levels were significantly reduced in all the MIA Paca-2 and PANC-1 clones. MRP5 affected gemcitabine cytotoxicity and the rate of gemcitabine-induced apoptosis. Silencing MRP5 decreased cell proliferation and migration in both MIA Paca-2 and PANC-1 cells. Docking studies showed high binding affinity of cGMP towards MRP5, indicating the potential of MRP5-mediated cGMP accumulation in the microenvironment. In conclusion, MRP5 has an important role in cancer proliferation and migration in addition to its drug efflux functions in two widely available pancreatic tumour cell lines (MIA Paca-2 and PANC-1).

The immune system plays a crucial role in defending the body against foreign invaders, and the balance of various polyunsaturated fatty acids, such as alpha-linolenic acid (ALA), eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA), can impact immune cell functions and overall immune responses. This study aimed to assess the effectiveness of mussel oil extracts in modulating inflammatory responses by analysing their effects on immune cell lines and cytokine expression. Four different mussel oil extracts were obtained using two extraction methods (organic solvent and supercritical CO2 extraction) from two tissue sources (fresh and commercial). These extracts were then tested at various concentrations on T lymphocyte (Jurkat) cells, monocytes, and macrophages (THP-1 and U-937). Cytokine levels were quantified using ELISA. The results showed that the solvent-extracted samples had a dose-dependent effect on tumour necrosis factor alpha (TNF-α) and interleukin-1 beta (IL-1β) cytokine secretion in THP-1 and U937 cells, with the extract from a commercial mussel powder being more efficient than the extract from fresh powder. However, supercritical CO2 samples showed elevated cytokine secretion levels despite their high omega-3 content. Furthermore, 100 ug/mL extract from fresh powder successfully reduced interleukin-2 (IL-2) secretion while maintaining cell viability after stimulation. The study demonstrated that solvent-extracted mussel oil can effectively regulate cytokine secretion, modulate immune cell activation, and alleviate inflammation. These findings offer valuable insights into using mussel oil extracts to treat inflammatory disorders and enhance immune responses.

The economic value and flavor of tea with different harvest periods vary greatly. Therefore, rapid discrimination and authentication are important for quality control and commercialization of tea. Nano-electrospray ionization mass spectrometry (Nano-ESI-MS) is an emerging technique in food authenticity and traceability due to the minimal sample preparation required and short analysis time. In this study, Nano-ESI-MS method was established for rapid discrimination and authentication of Lushan Yunwu tea (LYT). The results showed that Nano-ESIMS could not only effectively distinguishing LYT of different harvest periods but also differentiating Mingqian tea adulterated with 5% Yuhou tea and Autumn tea, respectively, with 58 and 17 compounds were considered as markers, respectively. The decision tree and linear discriminant analysis were used to identify the adulteration of tea with classification accuracy of models of training and validation sets were higher than 99.2% and 86.9%, respectively. Moreover, Nano-ESI-MS was used to track the changes of these compounds during tea processing, including amino acids, caffeine, and catechins. The Nano-ESI-MS method could be regarded as a powerful analytical tool for rapid discrimination and authentication of tea.

Background:Gemcitabine (Gem) is one of the first-line chemotherapy drugs for pancreatic cancer treatment. However, its short half-life in plasma and adverse effects limited its broader application. Methods:A novel Gem derivative (N4 -tetradecyloxycarbonyl gemcitabine, tcGem) was synthesized and encapsulated into liposomes (LipotcGem) to overcome the above shortcomings. Results:LipotcGem has been successfully formulated, with the average size of 115 nm, zeta potential values of -36 mV, encapsulation efficiency of up to 98%, and drug loading capacity of 8.1%. Compared to Gem, LipotcGem improved in vitro antitumor activity significantly, as evidenced by the lower IC50, the higher percentage of apoptotic cells, the stronger ability to inhibit cell migration and invasion due to the higher cellular accumulation (100 times). Additionally, the endocytosis of LipotcGem was mainly mediated by caveolae, and was then processed in the lysosome, where tcGem was released and hydrolyzed into Gem. LipotcGem inhibited tumor growth by 70% in subcutaneous xenograft model and 90% in orthotopic xenograft model, respectively. LipotcGem suppressed tumor metastasis and prolonged survival without perceptible systemic toxicity, which may be caused by the longer t1/2 in vivo (3.5 times, 5.23 vs 1.46 h) and more enrichment in tumor tissue (750 times). Conclusion:LipotcGem significantly increased the anti-tumor efficiency and decreased the toxicity for chemotherapy of pancreatic cancer.

SummaryThis study investigates the benefits of green‐lipped mussels containing bioavailable PUFAs and inflammation‐modulating oil extracts. The goal is to find the best method for extracting lipids from two types of raw materials with strong immunomodulatory, anti‐inflammatory and antioxidant properties using organic solvents and supercritical carbon dioxide (CO2) techniques. The lipid classes are analysed using TLC‐FID and GC–MS to detect FFAs, while DPPH determines antioxidant levels. The cytokine production of IL‐6 and TNF‐α in LPS‐stimulated mouse macrophages is measured using ELISA. The results show that while supercritical CO2 is the most effective method for extracting lipids, the content can vary depending on the source and technique. The major FFAs found include EPA, Palmitic acid, DHA, and Palmitoleic acid, with PUFAs, particularly omega 3, being the most dominant. Samples exhibit potent radical scavenging in 2000 μg mL−1, similar to ascorbic acid at 62.5 μg mL−1 (62.2 ± 15.36%). The cells release more TNF‐α than IL‐6, and solvent extraction was found to regulate the immune response more effectively. In conclusion, the extracts contain significant amounts of EPA/DHA and variable FFAs, suggesting potential anti‐inflammatory effects. However, further validation in alternative in vitro models is necessary.

In this study, the conformational properties of tertiary trifluoroacetamides in dibenzoazepine (1a and 1b) and benzodiazepine (2a and 2b) derivatives, which exist as equilibrated E- and Z-amide conformers in solution, were investigated by 1H and 19F NMR spectroscopy. In all cases, one of the methylene protons neighboring the nitrogen atom of the minor conformer showed a finely split pattern due to coupling with the trifluoromethyl fluorine atoms, as confirmed by 19F-decoupling experiments. One-dimensional (1D) and two-dimensional (2D) 1H–19F heteronuclear Overhauser spectroscopy (HOESY) experiments were performed to confirm whether these couplings are attributable to through-bond spin–spin couplings (TBCs) or through-space spin–spin couplings (TSCs). HOESY cross-peaks between CF3 (19F) and one of the CH2–N protons of the minor conformers indicate that the two nuclei are spatially close to each other, thus establishing the stereochemistry of the major (E-) and minor (Z-) conformers. The E-amide preferences of the trifluoroacetamides are consistent with the results of density functional theory calculations and X-ray crystallographic analyses. Furthermore, the otherwise incomprehensible 1H NMR spectra were accurately assigned using the HOESY-determined TSCs. The 1H NMR assignments of the E- and Z-methyl signals of N,N-dimethyl trifluoroacetamide, the simplest tertiary trifluoroacetamide, were revised for the first time in half a century.

Gemcitabine is a chemotherapeutic agent for pancreatic cancer treatment. It has also been demonstrated to inhibit human pancreatic cancer cell lines, MIA PaCa-2 and PANC-1. The aim of the present study was to investigate the suppressive effect of fucoxanthin, a marine carotenoid, in combination with gemcitabine on pancreatic cancer cells. MTT assays and cell cycle analysis using flow cytometry were performed to study the mechanism of action. The results revealed that combining a low dose of fucoxanthin with gemcitabine enhanced the cell viability of human embryonic kidney cells, 293, while a high dose of fucoxanthin enhanced the inhibitory effect of gemcitabine on the cell viability of this cell line. In addition, the enhanced effect of fucoxanthin on the inhibitory effect of gemcitabine on PANC-1 cells was significant (P<0.01). Fucoxanthin combined with gemcitabine also exerted significant enhancement of the anti-proliferation effect in MIA PaCa-2 cells in a concentration dependent manner (P<0.05), compared with gemcitabine treatment alone. In conclusion, fucoxanthin improved the cytotoxicity of gemcitabine on human pancreatic cancer cells at concentrations that were not cytotoxic to non-cancer cells. Thus, fucoxanthin has the potential to be used as an adjunct in pancreatic cancer treatment.

Breast cancer is now the most common cancer worldwide, and it is also the main cause of cancer-related death in women. Survival rates for female breast cancer have significantly improved due to early diagnosis and better treatment. Nevertheless, for patients with advanced or metastatic breast cancer, the survival rate is still low, reflecting a need for the development of new therapies. Mechanistic insights into metastatic breast cancer have provided excellent opportunities for developing novel therapeutic strategies. Although high-throughput approaches have identified several therapeutic targets in metastatic disease, some subtypes such as triple-negative breast cancer do not yet have an apparent tumor-specific receptor or pathway to target. Therefore, exploring new druggable targets in metastatic disease is a high clinical priority. In this review, we summarize the emerging intrinsic therapeutic targets for metastatic breast cancer, including cyclin D-dependent kinases CDK4 and CDK6, the PI3K/AKT/mTOR pathway, the insulin/IGF1R pathway, the EGFR/HER family, the JAK/STAT pathway, poly(ADP-ribose) polymerases (PARP), TROP-2, Src kinases, histone modification enzymes, activated growth factor receptors, androgen receptors, breast cancer stem cells, matrix metalloproteinases, and immune checkpoint proteins. We also review the latest development in breast cancer immunotherapy. Drugs that target these molecules/pathways are either already FDA-approved or currently being tested in clinical trials.

Chondrocyte behavior is critical in osteoarthritis (OA) progression and cartilage deterioration. Recent studies have shown that green-lipped mussel (GLM) oil extracts obtained through solvent extraction can regulate cytokine secretion in cell lines, potentially reducing inflammation and immune cell activation. This study investigates the effects of these extracts on human chondrocyte cell lines to understand their impact on osteoarthritis development. Chondrocyte cultures exposed to osteoarthritis-related inflammatory factors were treated with various concentrations of GLM oil. The results revealed that mussel oils, particularly a commercial mussel powder extract (SOLV.COM), enhance glucose uptake and protect chondrocyte cells. SOLV.COM effectively manages the release of inflammatory markers like interleukin-6 (IL-6) and matrix metalloproteinases-3 (MMP-3), showing increased deoxyglucose uptake. This study highlights the significant influence of extract choice on managing interleukin-6 (IL-6) secretion and cellular activation pathways, demonstrating the potential of SOLV.COM in managing osteoarthritis by controlling reactive oxygen production, regulating glucose metabolism, and inflammatory markers.