Search Results (4,091)

Pancreatic lipase (PL) inhibition is a promising dietary strategy for obesity management. In this study, the inhibitory mechanisms and structural basis of polyphenols extracted from different sugarcane fractions were investigated using in vitro enzyme assays, spectroscopy, and molecular docking analyses. PL inhibitory activity was evaluated using p-nitrophenyl laurate (pNPL) as the substrate, with all assays performed in triplicate and results statistically analyzed. Among the extracts, sugarcane peel polyphenols (SP) exhibited the strongest inhibition, with a half-maximal inhibitory concentration (IC₅₀) of 31.56 mg/mL, significantly lower than that of sugarcane juice polyphenols (SJ, 55.86 mg/mL) and sugarcane bagasse polyphenols (SB, 65.31 mg/mL). Enzyme kinetic analyses revealed a reversible mixed-type inhibition mechanism. In contrast to crude extracts, individual phenolic monomers showed substantially lower IC₅₀ values (0.13–1.33 mg/mL), highlighting the intrinsic dilution. Compositional analysis identified ferulic acid, gallic acid, chlorogenic acid, and schaftoside as key contributors to PL inhibition. Fourier transform infrared (FTIR) and fluorescence spectroscopy demonstrated that polyphenols altered PL secondary structure by modulating α-helix and β-sheet contents and perturbed the microenvironment of tryptophan (Trp) and tyrosine (Tyr) residues. Molecular docking further indicated that these compounds bind within or near the substrate-binding channel via hydrogen bonding and hydrophobic interactions, engaging critical residues including Ser152, His263, and Phe77, and potentially influencing conformational elements involved in active-site accessibility. Collectively, these results suggest that sugarcane, particularly its peel, represents a valuable natural source of PL inhibitors. Despite the relatively high IC₅₀ values of crude extracts, their inhibitory activity arises from multicomponent contributions and supports their potential application as dietary modulators of fat digestion rather than as pharmaceutical lipase inhibitors. Full article

Lung adenocarcinoma (LUAD) is the most common subtype of non-small cell lung cancer and remains a leading cause of cancer-related mortality worldwide. MicroRNAs (miRNAs) are critical regulators of tumor progression; however, the biological role and molecular mechanisms of miR-589-3p in LUAD remain unclear. In this study, the expression levels of miR-589-3p and WWC2 were analyzed using The Cancer Genome Atlas lung adenocarcinoma (TCGA-LUAD) datasets via the UALCAN platform. Flow cytometric apoptosis analysis and functional assays including CCK-8, colony formation, AO/EB staining, and Transwell invasion assays were performed in LUAD cell lines. The interaction between miR-589-3p and WWC2 was validated using dual-luciferase reporter assays, Western blotting, and rescue experiments. miR-589-3p expression was significantly elevated in LUAD tissues compared with normal lung tissues (p < 0.05) and was positively associated with an advanced tumor stage and lymph node metastasis (p < 0.05). Inhibition of miR-589-3p significantly suppressed proliferation and colony formation (p < 0.05), reduced invasive capacity (p < 0.05), and markedly increased apoptosis (p < 0.01) in LUAD cells. Dual-luciferase reporter assays confirmed WWC2 as a direct target of miR-589-3p, with miR-589-3p mimics significantly reducing WWC2 wild-type reporter activity (p < 0.05). WWC2 expression was significantly downregulated in LUAD tissues (p < 0.05), and WWC2 knockdown reversed the anti-proliferative, pro-apoptotic, and anti-invasive effects induced by miR-589-3p inhibition (p < 0.01). These findings demonstrate that miR-589-3p promotes lung adenocarcinoma progression by directly suppressing WWC2. The miR-589-3p/WWC2 axis represents a novel molecular mechanism contributing to LUAD malignancy and may provide a foundation for future mechanistic and translational studies. Full article

The abnormal activation of the Nlrp3 (Nod-like receptor pyrin 3) inflammasome, in response to oxidative stress or impaired antioxidant defense, is linked to aging-related diseases. Previously, we have shown that Peroxiredoxin (Prdx)6 deficiency triggers reactive oxygen species (ROS)-dependent activation of Kruppel-like factor (Klf)9/Nlrp3 inflammasome in aging lens epithelial cells (LECs). Herein, we test the therapeutic efficacy of Prdx6 delivery in abating the oxidative stress-induced aberrant activation of the Klf9/NF-ĸB/Nlrp3 pathway and subsequent pyroptotic cell death in LECs and Prdx6-deficient (Prdx6^−/−) LECs. Similar to aged LECs, Prdx6-depleted LECs exhibited activation of Nlrp3 inflammasome components—including ASC, Caspase-1, IL-1β, IL-18, GSDMD—and displayed heightened sensitivity to H₂O₂/ UVB-induced oxidative damage. The delivery of TAT-HA-Prdx6 or the overexpression of Prdx6 in Prdx6^−/− mLECs significantly suppressed the aberrant activation of these inflammatory components and restored redox balance by eliminating ROS levels during oxidative stress. Similarly, TAT-HA-Prdx6 effectively internalized into SRA-hLECs and suppressed the H₂O₂- and/or UVB-induced upregulation of Nlrp3 and its components. Furthermore, the oxidative stress or Prdx6 deficiency led to increased Nlrp3 promoter activity and NF-ĸB activation, accompanied by decreased cytosolic IĸBα and increased phosphorylation of IĸBα; these alterations were reversed by Prdx6 overexpression. The elevated Klf9 transcription observed in aging and Prdx6^−/− mLECs or under oxidative stress was also inhibited by Prdx6 delivery. Additionally, Prdx6^−/− mLECs and aging LECs displayed increased TXNIP and reduced TRX levels, which were normalized by Prdx6 restoration. Collectively, this study provides the first evidence that the loss of Prdx6 drives aberrant activation of Klf9/NF-ĸB/Nlrp3 inflammasome axis, leading to pyroptotic cell death. Prdx6 delivery represents a promising therapeutic strategy to rescue cells from pyroptosis (oxidative stress-induced inflammatory cell death). Full article

RNA degradation plays a vital role in post-transcriptional regulation of gene expression. RNA stability is changed in the pathogenesis of metabolic dysfunction-associated steatotic liver disease (MASLD), but its role and underlying mechanisms in sleeve gastrectomy (SG) effectively remodeling hepatocytes and improving MASLD is unclear. A high-fat diet-induced MASLD model for SG and a hepatocyte-specific Zfp36 knockdown mouse model were established to evaluate the role of zinc finger protein 36 (ZFP36) in MASLD. The expression of ZFP36 and TEA domain transcription factor 4 (TEAD4) was examined in liver tissue samples from MASLD patients. Hepatic ZFP36 expression is downregulated in MASLD but is restored following SG. Hepatocyte-specific Zfp36 knockdown exacerbates high-fat diet-induced liver injury and impairs the therapeutic effect of SG on hepatic steatosis. Mechanistically, ZFP36 binds to TEAD4 mRNA to promote its degradation, thereby modulating the Hippo pathway. Inhibition of TEAD4 transcriptional activity reverses the aggravated MASLD phenotype caused by Zfp36 knockdown. In liver biopsy samples from MASLD patients, ZFP36 expression correlates negatively with TEAD4 expression. Collectively, these findings identify SG-induced upregulation of ZFP36 as a critical mechanism for alleviating MASLD through suppression of TEAD4. Full article

Cannabis sativa is a multipurpose dioecious species whose crop performance is governed by sex expression. Although sex is genetically determined by an X/Y chromosome system, plants can develop flowers of the opposite sex through sex reversion, commonly induced by manipulating endogenous hormone levels using plant growth regulators (PGRs). Here, we evaluated the effectiveness of PGRs that promote or inhibit major hormone pathways implicated in plant sex expression. Male and female clones from two accessions were treated with foliar applications of nine PGRs and four combinatory treatments to assess sex- and genotype-specific responses. Floral biomass and the proportion of each sex were recorded at harvest to assess treatment effectiveness. Ethylene emerged as the primary regulator of chemically modulated sex reversion in C. sativa, with its inhibition by silver thiosulfate inducing strong female-to-male reversion and its promotion by ethephon inducing equally strong male-to-female reversion in the inflorescences. Gibberellin promotion on its own resulted in female-to-male reversion at the axial nodes only, while its inhibition showed no reciprocal effects. The combination of silver thiosulfate and gibberellic acid resulted in the most complete female-to-male reversion, and all sex-reverted flowers were fertile. Together, the results indicated that flowers at axial nodes and at the terminal ends of inflorescences are under different hormonal control. Cytokinins, auxins, and jasmonates were found to exert minimal influence on sex reversion. All treatments exhibited pleiotropic effects, particularly gibberellic acid and paclobutrazol, which altered resource allocation, shifting biomass away from and towards floral tissue, respectively. These findings advance our understanding of the hormonal regulation of sex expression in C. sativa and identify optimized approaches for its manipulation. Full article

Background: Midkine (MDK), a secreted heparin-binding growth factor, is involved in tumor progression and metastasis. While serum MDK is widely recognized as a potential prognostic biomarker for colorectal cancer (CRC), its specific functional role and underlying mechanisms in CRC development are not fully understood. Methods: The four publicly available CRC microarray datasets—GSE41258, GSE44076, GSE81558, and GSE117606—along with TCGA-COAD and TCGA-READ datasets and their associated clinical data were obtained. MDK expression was measured at both the mRNA and protein levels using quantitative real-time PCR (qRT-PCR) and Western blotting. To investigate its oncogenic functions, a comprehensive set of assays was performed: transwell and wound healing assays for invasion and migration; CCK-8 and colony formation assays for proliferation; and tail vein/spleen injection models combined with xenograft models to study metastasis and tumor growth in vivo. To uncover underlying mechanisms, Western blotting was used to examine the involvement of epithelial–mesenchymal transition (EMT) and the PI3K/AKT signaling pathway. Results: MDK is significantly overexpressed in CRC tissues and cells compared to normal tissues and cells. Notably, patients with high MDK levels show poorer overall survival (OS). Overexpression of MDK increases CRC invasion, migration, proliferation, and metastasis both in vivo and in vitro, while its knockdown reverses these effects. Mechanistically, MDK activates the PI3K/AKT pathway, leading to increased AP2A1 expression and promotion of EMT in CRC. Conclusions: MDK promotes invasion, migration, proliferation, metastasis, and EMT in CRC cells through the PI3K/AKT pathway by inducing AP2A1 expression, which could serve as a diagnostic marker. The PI3K inhibitor LY294002 significantly reduces AP2A1 levels and inhibits MDK-induced malignant behaviors. Targeting MDK-related signaling pathways may offer new strategies for CRC treatment. Full article

Apoptosis, or programmed cell death, is a fundamental process essential for tissue homeostasis, development, and the elimination of damaged or potentially cancerous cells. Here, we identify the E3/E4 ubiquitin ligase UBE4B as a critical suppressor of apoptosis in p53-proficient tumor cells, functioning through a previously uncharacterized dual mechanism. Initially, an orthogonal ubiquitin transfer screening approach identified CCAR2 as a UBE4B substrate. We demonstrate that UBE4B interacts with and ubiquitinates CCAR2, promoting its proteasomal degradation. Furthermore, we found that UBE4B concurrently targets p53 itself for ubiquitin-dependent degradation. Functionally, UBE4B overexpression suppresses apoptosis, whereas rescue experiments indicate that restoring p53 expression reverses this suppression more effectively than restoring CCAR2, highlighting the dominance of the direct p53 degradation pathway. Mechanistically, UBE4B deficiency leads to CCAR2 accumulation, which inhibits SIRT1 activity, thereby enhancing p53 acetylation and stability; this effect is reversed upon CCAR2 co-depletion. Consistently, transcriptional profiling confirms that UBE4B downregulates key p53 target genes (e.g., BAX, PUMA) through this dual-pathway regulation. In summary, our study establishes that UBE4B acts as a key apoptosis suppressor by coordinately degrading both p53 and its positive regulator CCAR2, revealing a targetable vulnerability in p53-wild-type tumors. Full article

Background: Electrochemotherapy enhances the intracellular delivery of anticancer agents through electroporation but is traditionally limited to cytotoxic drugs associated with significant side effects. Vitamin C (ascorbic acid) exhibits selective anticancer activity when accumulated at high intracellular concentrations; however, its therapeutic application is restricted by poor membrane permeability and rapid systemic clearance. Methods: In this study, we investigated whether reversible electroporation, applied using a custom-designed variable plate electrode system designed to deliver a uniform electric field, could potentiate the antitumor efficacy of low-dose vitamin C. Numerical simulations were performed to optimize electrode spacing and stimulation voltage, suggesting homogeneous electric field coverage throughout the tumor volume. The proposed approach was evaluated in vitro using MDA-MB-231 and 4T1 breast cancer cell lines and in vivo in a 4T1 murine breast cancer model. Results: Low-dose vitamin C alone produced minimal cytotoxic effects, whereas its combination with electroporation significantly reduced cell viability and increased apoptotic and necrotic cell death in vitro. In vivo, vitamin C–assisted electrochemotherapy resulted in pronounced tumor growth suppression, with tumor volumes reduced to approximately 0.34-fold of baseline by day 15, accompanied by decreased proliferation and marked tissue disruption. Conclusions: These findings demonstrate that uniform-field reversible electroporation markedly enhances the intracellular delivery and antitumor activity of low-dose vitamin C, supporting this technology-driven strategy as a promising, low-toxicity alternative to conventional chemotherapeutic agents in electrochemotherapy for solid tumors. Full article

The Morus genus comprises several tree species whose fruits are used in human nutrition, while the leaves and roots are used in traditional medicine. The aim of this study was to highlight the antioxidant, cholinesterase inhibitory, and neuroprotective effects of hydroalcoholic extracts from Morus alba (MAE) and Morus nigra (MNE) leaves. RP-UHPLC-PDA analysis of extracts revealed the presence of polyphenols in higher quantities in MNE extract compared to MAE. Both extracts demonstrated antioxidant properties in the hydroxyl radical scavenging and lipid peroxidation inhibition assays. MNE exhibited a superior antioxidant capacity compared to MAE; the IC₅₀ values for the inhibition of plasma lipid oxidation assay were 25.31 ± 2.54 µg/mL for MNE and 29.85 ± 0.97 µg/mL for MAE. Both extracts showed cholinesterase inhibitory activity. The IC₅₀ values for acetylcholinesterase inhibition were 24.34 ± 0.86 µg/mL for MNE and 46.87 ± 2.16 µg/mL for MAE. The inhibitory potency of MNE was comparable to that of galantamine, which was used as standard. Both extracts reversed, in a dose-dependent manner, the scopolamine-induced cognitive impairment and behavioural alterations in scopolamine-treated zebrafish (Danio rerio) as evaluated by the Y-maze test, novel tank diving test, and novel object recognition test. Full article

Kynurenic acid (KYNA), a metabolite of the L-kynurenine pathway of L-tryptophan degradation, is an endogenous blocker of glutamate ionotropic excitatory amino acid (EAA) receptors and nicotinic acetylcholine receptors (nAChRs). KYNA plays a significant role in various neuropsychiatric disorders and the aging process. Some researchers have suggested that KYNA may contribute to memory impairment. In this study, we examined the impact of L-kynurenine (a KYNA substrate) and the anti-dementia drugs D-cycloserine and Cerebrolysin on kynurenine aminotransferase (KAT) activity, an enzyme forming KYNA, in liver homogenates of Helix pomatia snails. Furthermore, a memory model was established using these snails, wherein tentacle shortening served as an indicator of learning activity. In vitro experiments on Helix pomatia demonstrated the significant impact of L-kynurenine and anti-dementia drugs on KYNA synthesis. KYNA levels increased significantly in the presence of L-kynurenine in liver homogenate. However, KYNA formation decreased when anti-dementia drugs, including Cerebrolysin or D-cycloserine, were administered to the snails’ liver homogenate. L-kynurenine has been shown to impair the learning process in vivo in snails, but an anti-dementia drug has been demonstrated to reverse this effect. Significant inhibition of tentacle lowering was observed in response to L-kynurenine treatment, which corresponded with elevated KYNA levels in the central nervous system. Administering D-cycloserine or Cerebrolysin alongside L-kynurenine reversed its effects. The Helix pomatia memory model is a valuable tool for studying learning and memory formation in various conditions and in the presence of different pharmacological agents. A drug or natural extract that blocks KYNA synthesis has the ability to increase tentacle lowering and could be considered an anti-dementia agent. Furthermore, this metabolite may also protect against aging and delay damage to the central nervous system related to memory. Full article

Atopic dermatitis (AD) is a chronic inflammatory dermatosis driven by skin barrier dysfunction, immune dysregulation, and gut–skin axis imbalance. While probiotics show promise, the therapeutic potential and mechanisms of topical postbiotics in modulating the gut–skin axis remain understudied. Here, we investigated the efficacy of Schleiferilactobacillus harbinensis JNDM-derived cell-free supernatant (CFS) and lysate (ShL) in a DNFB-induced AD mouse model. Topical application of both CFS and ShL significantly attenuated AD-like symptoms, reduced epidermal thickening, and restored the expression of the barrier protein filaggrin. Immunologically, treatment suppressed the Th2-dominant inflammatory cascade (IL-4, IL-5, IL-13, IL-33, TSLP) and reduced serum IgE and IFN-γ levels. Notably, ShL exhibited superior systemic efficacy, significantly inhibiting mast cell infiltration and reducing the spleen index. 16S rRNA sequencing revealed that topical intervention remotely remodeled the gut microbiota, specifically reversing the depletion of the beneficial genus Alistipes and suppressing the compensatory increase in Odoribacter. This microbial restructuring was accompanied by distinct metabolic changes: ShL treatment resulted in an approximately 4-fold elevation in fecal butyrate concentrations compared with the model group. Correlation analysis further validated a strong positive axis linking Alistipes abundance and butyrate levels to skin barrier integrity. Collectively, our findings demonstrate that S. harbinensis postbiotics—particularly the lysate—ameliorate AD through a dual mechanism of local barrier repair and systemic metabolic modulation via the gut–skin axis, presenting a promising non-steroidal therapeutic strategy. Full article

Background: Gastric cancer (GC) is characterized by aggressive invasion and early peritoneal dissemination, which are strongly driven by chronic inflammation and epithelial–mesenchymal transition (EMT). c-Jun N-terminal kinase (JNK), a stress-responsive serine/threonine kinase within the mitogen-activated protein kinase (MAPK) family, integrates inflammatory cues to promote EMT and metastasis. Huangjin Shuangshen granules (HJSS) is a multi-component traditional Chinese medicine (TCM) formula derived from Simiao Yong’an Decoction and clinically used as an adjuvant therapy for GC. However, whether HJSS restrains inflammation-driven metastasis through modulation of JNK-associated EMT signaling remains unclear. Methods: The anti-metastatic efficacy of HJSS was evaluated using integrated in vivo and in vitro models, combined with transcriptomics, network pharmacology and molecular validation. Results: HJSS markedly attenuated LPS-induced metastatic behavior and inflammatory activation. Multilevel analyses converged on MAPK8/JNK as a central regulatory node. HJSS reversed EMT progression and inhibited nuclear phosphorylation of JNK without affecting its upstream kinases. Thermal-shift assays and molecular docking supported potential target engagement of HJSS-derived constituents, including possible interactions with JNK-related signaling targets. Pharmacologic reactivation of JNK partially abrogated the inhibitory effects of HJSS, confirming JNK-dependent action. Conclusions: HJSS suppresses inflammation-driven GC metastasis primarily by attenuating JNK-associated EMT, potentially through modulation of JNK activation by its bioactive constituents. These findings provide mechanistic insight into HJSS as a low-toxicity anti-metastatic strategy and support further exploration of its active constituents. Full article

Human adipose biology is strongly influenced by three-dimensional (3D) architecture, cell–cell interactions, and local oxygen availability maintained over a long-term culture period, features that are not reproduced in traditional two-dimensional (2D) culture systems. To address this gap, we established a long-term human adipose-derived stem cell (hASC) spheroid model using elastin-like polypeptide–polyethyleneimine (ELP-PEI) coating. The ELP-PEI coating facilitated stable spheroid formation and sustained adipogenic differentiation over 56 days. As spheroids enlarged and matured, they exhibited hallmark features of adipocytes, including lipid accumulation, morphological compaction, and transition out of the proliferative state. Glucose uptake increased during maturation and declined as spheroids became larger. This reduction coincided with a marked rise in hypoxia-inducible factor-1α (HIF-1α) expression, indicating the emergence of a hypoxic microenvironment within larger spheroids. Notably, inhibiting HIF-1α restored insulin-stimulated glucose uptake, demonstrating that hypoxia was the primary driver of impaired insulin responsiveness in late-stage spheroids. These findings position ELP-PEI-supported hASC spheroids as a practical and physiologically relevant platform for studying human adipocyte biology, particularly the development and reversibility of hypoxia-associated metabolic dysfunction. This model offers new opportunities for mechanistic studies and for evaluating therapeutic strategies targeting insulin resistance and adipose tissue pathology. Full article

Background: Dental caries remains one of the most prevalent oral diseases worldwide, largely driven by the virulence of Streptococcus mutans. Although plant phenolics from green tea and pomegranate are known for their antimicrobial properties, their molecular mechanisms of action against key S. mutans virulence targets remain insufficiently characterized. Aim: This study investigated the antibacterial and anti-virulence properties of Viroelixir, a phenolic-rich formulation derived from green tea (Camellia sinensis) and pomegranate (Punica granatum), against S. mutans, with particular emphasis on predictive molecular docking interactions with critical virulence-associated proteins. Methods: Viroelixir phytochemical composition was characterized by LC–MS using a C18 reverse-phase column and negative electrospray ionization mode. Antibacterial activity was evaluated using growth kinetics, agar plating, and crystal violet assays. Acidogenicity, hemolytic activity, and biofilm formation were assessed using pH modulation, hemolysis assays, SEM, and biofilm biomass quantification. Virulence gene expression was analyzed by RT-qPCR. In silico molecular docking was performed to explore potential interactions between major LC–MS-supported phenolic constituents and S. mutans virulence proteins, including glucosyltransferase B (GtfB), LuxS, and SpaP. Biocompatibility was evaluated in human gingival epithelial cells. Results: The LC-MS analysis revealed a complex mixture of phenolic compounds consistent with catechins and ellagitannins. Compound identification was considered tentative and based on mass spectral range and chromatographic behavior. Viroelixir significantly inhibited S. mutans growth, acid production, hemolytic activity, and biofilm formation in a concentration-dependent manner. Key virulence genes were markedly downregulated. Docking analyses suggested stable binding of selected phenolics—particularly punicalagin, catechin, and epigallocatechin—within the active sites of GtfB, LuxS, and SpaP. Importantly, Viroelixir showed no cytotoxic effects on gingival epithelial cells. Conclusions: Viroelixir exerts potent antibacterial and anti-virulence effects against S. mutans through a multi-target mechanism combining transcriptional suppression and predictive molecular inhibition of virulence proteins, supporting its potential as a safe, natural therapeutic for caries prevention. Full article

Background: Dodder, the dried mature seed of Cuscuta chinensis Lam. (CCL), has demonstrated anti-tumor activity, but its molecular and immunological mechanisms in clear cell renal cell carcinoma (ccRCC) remain unclear. Objective: To identify potential targets and elucidate the immune mechanisms by which CCL exerts therapeutic effects against ccRCC. Methods: A network pharmacology approach was employed to predict CCL’s bioactive components and their putative targets in ccRCC. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were used to explore relevant pathways. Molecular docking validated the binding of key compounds to hub proteins. In vitro assays—including cell viability, colony formation, invasion, and apoptosis measurements—assessed the effects of quercetin, a principal CCL constituent, on 786-O renal carcinoma cells. Flow cytometry was performed to determine the percentage of CD163⁺ cells. An in vivo xenograft model evaluated CCL’s anti-tumor efficacy. Western blotting, flow cytometry, and multiplex immunohistochemistry (mIHC) examined the modulation of signaling pathways and immune cell markers. Results: Network pharmacology identified IL-6, EGFR, TLR4, MMP9, CD44, and IFN-γ as core targets of CCL in ccRCC. Enrichment analyses implicated immune regulation, inflammation modulation, and PI3K/AKT signaling inhibition. Molecular docking revealed strong quercetin–MMP9 binding affinity. Immuno-correlation analyses indicated that high MMP9 levels positively correlated with macrophage infiltration and M2 polarization, suggesting a role in tumor immune escape. Quercetin significantly reduced the viability of 786-O cells in a dose-dependent manner, showing approximately 45% inhibition at 80 μM (p < 0.01). In addition, quercetin decreased MMP9 expression and reduced the proportion of CD163-positive macrophages. These effects were reversed by FSL-1 TFA (Toll-like receptor 2/6 agonist), which is the agonist of MMP-9. In the xenograft model, tumor volume in the quercetin-treated group was reduced by approximately 50% compared with the control group. Conclusions: CCL, particularly its active component quercetin, may inhibit ccRCC progression via inhibiting MMP9-mediated M2 macrophage polarization. Full article