Search Results (18,126)

MicroRNAs (miRNAs) are critical regulators of gene expression in cancer biology and cardiovascular disease. miR-106b-5p, a member of the miR-106b-25 cluster, has been widely studied for its oncogenic activity in various malignancies. However, its role as a direct molecular driver of anthracycline-induced cardiotoxicity has only recently been uncovered. This finding highlights new therapeutic possibilities at the intersection of oncology and cardiovascular medicine. This review outlines the dual role of miR-106b-5p as a key modulator in both tumor progression and chemotherapy-induced cardiac dysfunction. miR-106b-5p is upregulated in numerous cancers—including breast, prostate, lung, gastric, colorectal, hepatocellular, and esophageal—and promotes tumorigenesis via suppression of tumor suppressors such as PTEN, BTG3, p21, and SMAD7, leading to activation of oncogenic pathways like PI3K/AKT and TGF-β. Importantly, we present the first evidence that miR-106b-5p is significantly upregulated in the myocardium in response to doxorubicin treatment, where it drives left ventricular dysfunction by targeting PR55α, a key regulator of PP2A activity. This pathway results in cytoplasmic HDAC4 accumulation, aberrant activation of the YY1 transcription factor, and upregulation of sST2, a biomarker linked to adverse cardiac remodeling and poor prognosis. In response, we developed AM106, a novel locked nucleic acid antagomir that silences miR-106 b-5p. Preclinical studies demonstrate that AM106 restores PR55α/PP2A activity, reduces sST2 expression, and prevents structural and functional cardiac damage without compromising anti-tumor efficacy. In parallel, artificial intelligence (AI) tools could be leveraged in the future—based on established AI applications in miRNA cancer research—to accelerate the identification of miR-106b-5p-related biomarkers and guide personalized therapy selection. Our findings position miR-106b-5p as a previously unrecognized molecular bridge between cancer and doxorubicin-induced cardiotoxicity. The development of the AM106 antagomir represents a promising approach with potential clinical applicability in cardio-oncology, offering dual benefits: tumor control and cardioprotection. Coupling this innovation with AI-driven analysis of patient data may enable precision risk stratification, early intervention, and improved outcomes. miR-106b-5p thus emerges as a central therapeutic target and biomarker candidate for transforming the clinical management of cancer patients at risk for heart failure. Full article

Background: This study addresses an important vulnerability in the treatment of high-risk neuroblastoma (NB). NB is characterized by high rates of metastasis, drug resistance, relapse, and treatment-related toxicities. Current treatments, which include intensive chemotherapy, surgical removal of tumors, and stem cell transplants, have less than 50 percent survival rates among high-risk NB patients, demonstrating the need for novel targeted treatment approaches. CXC chemokine receptor 2 (CXCR2), a G-protein-coupled receptor, has been implicated in promoting cancer cell proliferation, invasion, metastasis, angiogenesis, chemoresistance, and maintaining cancer stem cells. Methods: We analyzed transcriptomic data from 1,464 primary NB patient samples to evaluate the prognostic significance of CXCR2 expression. Pharmacological inhibition of CXCR2 using SB225002, a selective small-molecule antagonist, was evaluated to determine its effects on cell growth, colony formation, apoptosis, and cell cycle progression in different NB cell lines. Three-dimensional (3D) spheroid models were used to examine tumor growth under physiologically relevant conditions. Mechanistic studies included gene expression analyses and immunoblot validation of key signaling regulators. Results: High CXCR2 expression was found to be inversely correlated with overall survival in patient datasets, suggesting a role in NB pathogenesis. Treatment with SB225002 significantly inhibited NB proliferation and colony formation while inducing apoptosis and cell cycle arrest in a dose-dependent manner. In 3D spheroid models, SB225002 significantly impaired spheroid formation and growth, confirming its potent anti-tumor efficacy. Mechanistically, CXCR2 blockade inhibited the expression of key pathway targets, including GLIPR1, BACH2, JUN, CHEK1, AKT1, and CXCR2 itself. Immunoblot analysis confirmed significant inhibition of CXCR2 and GLIPR1 protein levels in response to SB225002 treatment. Conclusions: Taken together, our findings demonstrate that pharmacological inhibition of CXCR2 using SB225002 effectively inhibits NB tumor cell growth and tumorigenicity by modulating oncogenic signaling networks. This study provides strong evidence for elucidating CXCR2-targeted therapies as an attractive treatment option for NB. These findings support the development of CXCR2-targeted therapies for high-risk NB. Full article

The tumor microenvironment (TME) is characterized by hypoxia; acidic pH; oxidative stress; and immune suppression; all of which severely impair the efficacy of conventional cancer therapies. Recent advances in inorganic nanotechnology have led to the development of smart nanomaterials capable of modulating these abnormal features; thereby reprogramming the TME toward a more therapy-responsive state. Inorganic nanomaterials such as manganese dioxide; iron oxide; and cerium oxide can selectively alleviate hypoxia; buffer acidity; regulate redox balance; and even stimulate anti-tumor immunity through catalytic or structural mechanisms. These materials can further serve as carriers for stimuli-responsive drug delivery; enabling synergistic therapies that include chemodynamic; photothermal; and immunomodulatory treatments. This review summarizes recent developments in smart inorganic nanomaterials for TME modulation; discusses design considerations including biosafety and biodegradability; and evaluates the current translational status and future directions. Such strategies represent a promising leap toward precise and personalized cancer nanomedicine Full article

Background/Objectives: Cancer is a worldwide health concern and is the second leading cause of death, responsible for nearly one in six deaths. Discovery of new anticancer agents is still a challenge for medicinal chemists and further research will improve patients’ chances of survival. Protein kinases are among the most popular and successful biological targets for developing anticancer drugs. In this context, protein kinases were selected as targets, and a series of isatin–quinazoline hybrids were synthesized. Methods: Their antiproliferative activity was evaluated against four cancer cell lines (HepG2, MCF-7, MDA-MB-231, and HeLa) and one normal fibroblast cell line (WI38) using MTT assays. Results: The tested compounds showed variable cytotoxic effects on the four cancer cell lines. Compound 6c exhibited the most potent anticancer activity against all cancer cells. In addition, this compound was tested for the effect on the expression of anti-apoptotic Bcl-2 protein and pro-apoptotic proteins Bax, caspase-3, and caspase-9, which revealed induction of apoptosis similar to staurosporine. Furthermore, an annexin V-FITC/PI dual staining assay confirmed that compound 6c induced cell death by apoptosis. Flow cytometric analysis revealed that compound 6c induced cell cycle arrest at the sub-G1 and S phases in the HepG2 cell line. Moreover, compound 6c was found to be a multi-kinase inhibitor with potent inhibitory activity on CDK2, EGFR, VEGFR-2, and HER2, with IC₅₀ values of 0.183 ± 0.01, 0.083 ± 0.005, 0.076 ± 0.004, and 0.138 ± 0.07 μM, respectively. Finally, a molecular docking simulation was conducted to predict possible binding interactions with the active site of CDK2. Conclusions: These findings suggest that compound 6c is a promising multi-kinase inhibitor with potent anticancer activity, warranting further investigation as a potential therapeutic agent. Full article

Cryptotanshinone (CPT), the main active compound of Salvia miltiorrhiza, is known for its anti-inflammatory, antioxidative, and antifibrotic effects. In this study, the hepatoprotective effect and mechanisms of CPT were explored using transcriptome and network pharmacology. A carbon tetrachloride-induced acute liver injury (ALI) mouse model was established. The anti-ALI effects of different doses of CPT were evaluated by analysis of biochemical indicators, histopathological staining, and immunohistochemical analysis. Combining network pharmacology with transcriptomic analysis revealed therapeutic targets, which were subsequently validated through polymerase chain reaction and Western blotting. CPT (40 mg/kg) treatment significantly reduced the levels of aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, tumor necrosis factor-α, interleukin-6, and interleukin-1β in model mice and regulated oxidative stress indicators, including malonaldehyde, superoxide dismutase, glutathione, and catalase. MCP-1 protein expression in the liver was inhibited by treatment with CPT. Network pharmacology revealed 72 core targets involved in the treatment of ALI by CPT. By combining transcriptomic data from liver tissue, three key targets—TNF-α, TLR9, and ADORA2B—were identified, along with the TLR, IL-17, and TNF signaling pathways. Furthermore, PCR and Western blot assays revealed that CPT significantly decreased TNF-α, TLR9, and ADORA2B expression levels in the livers of ALI mice. In conclusion, the hepatoprotective effects of CPT may be related to the suppression of TNF-α-, TLR9-, and ADORA2B-mediated inflammation, oxidative stress, and apoptosis. These results provide a foundation for the development of CPT as a potential therapeutic agent for ALI. Full article

Dendritic cells (DCs) are the most highlighted cell population for cancer immunotherapy development. Currently, DC-derived exosomes show promising anti-cancer activity. Exosomes are a subpopulation of extracellular vesicles (EVs) and originate from endosomes. It transports dynamic molecular cargos such as DNA, RNA, protein, and lipid. This cellular cargo exchange reprograms the recipient cell naturally. In cancer research, DC-derived exosomes (DEXs) are used as a therapeutic tool. There are some approaches followed in the application of DEX in cancer as a therapeutic tool. DEX-based drug delivery, tumor antigen-loaded DEX, and modified DEX are applicable approaches in cancer therapy. DEXs are biocompatible, nontoxic, and have ability-specific targeting. On the other hand, this method faces some challenges, such as large-scale production, isolation, and heterogeneity. A multidisciplinary approach (advanced nanotechnology, multi-omics, and single-exosome profiling) comes up with a solution to this issue. This review provides a comprehensive overview of the DEX approach, tracing its developmental journey and therapeutic application in cancer immunotherapy. It examines key findings from clinical trials and outlines the challenges and future research directions in this field, ultimately underscoring the potential of DC-derived exosomes as a research-backed, cell-free solution for the next generation of cancer immunotherapies. Full article

A three-dimensional quantitative structure-activity relationship (3D-QSAR) analysis incorporating ligand-receptor docking alignment and molecular dynamic (MD) simulations was conducted to elucidate the potent inhibitory effects of a series of benzamide derivatives on histone deacetylase 1 (HDAC1). A comparison between ligand-based (LB) and receptor-based (RB) 3D-QSAR models using molecular docking alignment produced statistically significant results. Steric and electrostatic contour maps provided insights into the interactions surrounding the benzamide ring, revealing that an increase in electron density enhances inhibitory activity. Furthermore, MD simulations were employed to investigate protein-ligand interactions in greater detail, yielding outcomes consistent with those from 3D-QSAR and molecular docking studies. This integrated approach of molecular docking, 3D-QSAR, and energy decomposition analysis derived from MD simulations, provides a valuable framework for the rational design of more potent HDAC1 inhibitors, facilitating the synthesis of highly effective anti-tumor compounds based on benzamide scaffolds. Full article

In this study, we report the synthesis of three new derivatives of betulinic acid, a pentacyclic triterpenoid known for its antitumor activity. These derivatives were synthesized via amide bond formation at the C-28 position using 3-[(Ethylimino)methylidene]amino-N,N-dimethylpropan-1-amine (EDC)/Hydroxybenzotriazole (HOBt) activation and various amines as nucleophiles. The synthesized compounds were characterized by nuclear magnetic resonance (NMR) techniques, including proton (¹H), carbon-13 (¹³C), COSY, HSQC, and DEPT, as well as ultraviolet–visible (UV-VIS) spectroscopy, Fourier-transform infrared (IR) and elemental analysis. This work highlights the potential of semi-synthetic modification of betulinic acid to enhance anticancer properties while addressing challenges in solubility and bioavailability. Further structural optimization and formulation studies are warranted to improve drug-like properties and therapeutic applicability. Full article

Jin’er (Naematelia aurantialba), commonly known as golden ear, is a traditional edible fungus that has long been recognized for its medicinal and culinary properties in China. Recently, it has been registered as a new cosmetic ingredient, drawing significant attention across various fields, including medicine, food, and cosmetics, due to its array of nutritional and medicinal benefits. N. aurantialba is rich in bioactive compounds, such as polysaccharides, dietary fiber, polyphenols, and active peptides. Among these, N. aurantialba polysaccharides (NAPs) are the primary active components, exhibiting a range of biological properties, including antioxidant, hypoglycemic, immunomodulatory, intestinal flora modulatory, anti-tumor, and anti-inflammatory effects. This comprehensive review summarizes the latest advancements in the extraction, purification, structural characteristics, functional activity, and related functional mechanisms of NAPs, as well as their industrial applications. Additionally, it discusses the current limitations in NAPs research and explores its potential future research directions. This review aims to provide up-to-date information and valuable references for researchers and industry professionals interested in the potential application of NAPs in the fields of food, medicine, healthcare, and cosmetics. Full article

Background/Objectives: T cell dysfunction represents a fundamental barrier to effective cancer immunotherapy. Although immune checkpoint blockades and adoptive cell transfer have achieved clinical success, therapeutic resistance remains prevalent across cancer types. Thymopentin (TP5), a synthetic immunomodulatory pentapeptide (Arg-Lys-Asp-Val-Tyr), has demonstrated immunostimulatory properties, yet its anticancer potential remains unexplored. The aim of this study was to investigate TP5’s antitumor efficacy and underlying immunological mechanisms. Methods: We evaluated TP5’s therapeutic effects in multiple murine tumor models, including B16-F10 melanoma, MC38 colorectal carcinoma, Hepa 1-6, and LM3 hepatocellular carcinoma. Immune cell populations and functional states were characterized using flow cytometry, ELISAs, and immunofluorescence analyses. The potential of TP5 as an adjuvant for T cell-based therapies was also systematically assessed. Results: The TP5 treatment markedly suppressed tumor growth across caner models through strictly T cell-dependent mechanisms. Critically, TP5 promoted thymic rejuvenation under immunocompromised conditions, restoring the thymus–tumor immunological balance and revitalizing peripheral T cell immunity. TP5 functionally reprogrammed T cell states, preserving effector function while ameliorating exhaustion. Furthermore, TP5 demonstrated synergistic efficacy when combined with adoptive T cell therapies, enhancing both proliferation and effector functions. Conclusions: TP5 represents a promising immunomodulator that addresses fundamental limitations of current T cell therapies by simultaneously enhancing T cell function and reversing thymic involution under immunocompromised conditions. Our findings provide compelling evidence for TP5’s clinical translation in cancer treatment. Full article

Tumor-infiltrating lymphocytes (TILs) are thought to play important roles in tumor shrinkage and survival prolongation in patients with breast cancer receiving neoadjuvant chemotherapy (NAC). TILs are mononuclear immune cells such as lymphocytes and plasma cells, including CD4+ and CD8+ T cells, natural killer cells, B cells, macrophages, regulatory T cells (Tregs), and myeloid/dendritic cells. The pre-NAC presence of more T cells and fewer Tregs in biopsy samples of primary breast tumors is known to contribute to tumor shrinkage and prolonged survival. This review was conducted to elucidate these roles in patients with breast cancer treated with NAC. Publications selected for inclusion in this review were identified by a PubMed search for articles published in English, performed using the terms “breast cancer”, “neoadjuvant chemotherapy”, “tumor-infiltrating lymphocyte”, “pathological complete response”, and “immune response”. The search was completed in July 2024. The functional roles of TILs in the achievement of these outcomes may vary by tumor subtype; increases and decreases in TIL levels before and after NAC have been shown to have conflicting effects. Biomarkers have been reported to predict local responses in the tumor microenvironment (e.g., immune-related gene signatures) and systemic immune responses (e.g., neutrophil-to-lymphocyte and platelet-to-lymphocyte ratios). Immune gene signatures and immune cell infiltration do not appear to be universally associated with tumor response or outcome in patients with breast cancer treated with NAC. The functional roles of TILs in breast tumor response and breast cancer survival may vary by tumor subtype, and conflicting results for the same subtypes may be due to differences in NAC regimens, immune responses, tumor heterogeneity, sample size, and the technical methods used to evaluate TILs in tumor samples. Full article

Polyporusterone B, a triterpene carboxylic acid isolated from Polyporus umbellatus Fries, exhibits anti-cancer and anti-hemolytic activities; however, its anti-inflammatory properties and underlying mechanisms remain unelucidated. We studied the anti-inflammatory effects of Polyporusterone B using lipopolysaccharide (LPS)-stimulated Raw264.7 murine macrophages (in vitro) and LPS-induced endotoxin shock in C57BL/6 mice (in vivo). Results showed that Polyporusterone B (1, 5, and 10 μM) had no cytotoxicity toward Raw264.7 cells, but significantly inhibited LPS-induced production of nitric oxide (NO) and pro-inflammatory cytokines (tumor necrosis factor (TNF-α), interleukin 1β (IL-1β), and interleukin 6 (IL-6)) in a concentration- and time-dependent manner, as demonstrated by Griess assay, qPCR, and ELISA. Western blot analysis revealed that Polyporusterone B suppressed LPS-induced phosphorylation of mitogen-activated protein kinases (ERK, P38, and NK) and reduced phosphorylation-mediated degradation of inhibitor of κBα (IκBα). Immunofluorescence and immunohistochemical staining further confirmed that Polyporusterone B blocked nuclear translocation of nuclear factor kappa-B (NF-κB)/Rel A in both Raw264.7 cells and mouse tissues. In the in vivo model, Polyporusterone B pretreatment significantly mitigated LPS-induced multi-organ pathological damage (e.g., lung edema, hepatic inflammation, renal hemorrhage) and downregulated tissue levels of TNF-α, IL-1β, and IL-6. These findings suggest that Polyporusterone B exerts anti-inflammatory effects by inhibiting the mitogen-activated protein kinase (MAPK) and NF-κB signaling pathways, suggesting its potential as a therapeutic candidate for inflammatory diseases. Full article

Cholangiocarcinoma (CCA) is an aggressive malignancy of the biliary tract with rising global incidence and limited treatment options. Its pathogenesis involves a complex interplay of genetic mutations, epigenetic dysregulation, inflammatory signaling, and environmental influences. Emerging evidence highlights the pivotal role of the gut–liver axis and microbiota dysbiosis in shaping biliary homeostasis and disease progression. Alterations in microbial composition disrupt apoptosis and autophagy, two key processes regulating cell survival and death, thereby contributing to tumorigenesis, metastasis, and therapy resistance. Specific taxa, including Enterococcus, Escherichia coli, Pseudomonas, Bifidobacterium, and Bacillus, demonstrate strain-dependent effects, acting either as tumor promoters through genotoxic metabolites and immune evasion or as potential tumor suppressors by inducing apoptosis and immune activation. These findings underscore the context-dependent roles of microbiota in CCA biology. Importantly, microbiota modulation offers novel therapeutic opportunities. Dietary interventions such as probiotics, prebiotics, and nutritional strategies, alongside innovative microbiome-targeted therapies, hold promise for restoring microbial balance, enhancing antitumor immunity, and improving patient outcomes. This review integrates current molecular and microbiological evidence to propose the gut microbiota as both a biomarker and a therapeutic target in CCA, opening avenues for precision medicine approaches in hepatobiliary oncology. Full article

Background: Gallic acid (GA) is a dietary polyphenol widely found in walnuts, tea leaves, and grapes, and it is recognized for its potent antioxidant and anti-inflammatory properties. Chronic sleep deprivation (CSD) is known to disrupt redox balance, promote neuroinflammation, and impair cognition, while effective nutritional strategies to mitigate these effects remain scarce. This study was designed to evaluate the protective potential of GA against CSD-induced cognitive deficits in mice and to elucidate the underlying mechanisms. Methods: Seventy-two male ICR mice were randomly allocated to six groups, including control, CSD model, Ginkgo biloba extract, and GA at three doses (50, 100, and 200 mg/kg). After 28 days of treatment, cognitive performance was assessed using the open field test (OFT), novel object recognition (NOR), step-through passive avoidance (ST), and Morris water maze (MWM). Redox status and inflammatory mediators were determined by ELISA, while the hippocampal expression of proteins related to antioxidant defense and NF-κB signaling was analyzed by Western blotting. Results: GA supplementation improved exploratory activity, recognition memory, and spatial learning in the CSD mice. Biochemical evaluation revealed that total antioxidant capacity (T-AOC) and superoxide dismutase (SOD) activity were restored, while malondialdehyde (MDA) levels, an indicator of lipid peroxidation, were reduced. These changes were accompanied by decreased circulating concentrations of interleukin-1β (IL-1β), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α). At the molecular level, GA enhanced the expression of Nrf2, HO-1, and NQO1, while inhibiting p-p65, iNOS, and COX2 in the hippocampus. Conclusions: These findings demonstrate that GA alleviates CSD-induced cognitive deficits through the activation of the Nrf2/HO-1 antioxidant pathway and inhibition of NF-κB–mediated inflammatory responses. Thus, GA may represent a promising nutraceutical candidate for maintaining cognitive health under chronic sleep loss. Full article

G-quadruplexes have been identified as a promising anti-cancer target because of their ability to modulate the stability of mRNAs encoding oncogenes, tumor suppressor genes, and other potential therapeutic targets. Deregulation of DNA damage and Unfolded Protein Response pathways in cancer cells may create vulnerabilities that can be exploited therapeutically. Previous studies have shown variations in the relative expression of DDR and UPR components in canine lymphoma and leukemia cell lines CLBL-1, CLB70, and GL-1. In the present study, we report the presence of G-quadruplex structures in these canine cell lines. Downregulation of the expression of DDR and UPR components at the mRNA level was observed in the CLBL-1 and CLB70 cell lines after stabilization of G4 structures using the ligand PhenDC3. In contrast, in GL-1 cells, important components of the DDR pathway, such as PARP1, GADD45A, and PIK3CB were upregulated in response to PhenDC3 treatment. Downregulation of DDIT4 mRNA expression, which encodes an important UPR component, was detected in the CLBL-1 and GL-1 cell lines after PhenDC3 exposure. These results suggest that G4 structures can be used to manipulate the expression of potential targets to treat lymphoma in dogs. A substantial enrichment of DNA replication and pyrimidine metabolism pathways was found in the GL-1 cell line after G4 stabilization. This finding suggests that PhenDC3 may induce DNA replication stress in this cell line. Collectively, these results support the feasibility of employing canine cancer cells as a model system to investigate the role of G-quadruplex structures in cancer. Full article