Search Results (5,458)

The clinical success rate of titanium (Ti) implants is significantly reduced in elderly patients and by implant-associated bacterial infections. Thus, Ti surfaces were modified using sandblasted large-grit alkaline etching (SLA), argon-nonthermal plasma treatment, and recombinant human secretory leukocyte protease inhibitor (rhSLPI) coating. This study evaluated surface characteristics, human fetal osteoblast (hFOB 1.19) activities, and antibacterial efficacy. The modified surfaces exhibited increased roughness and hydrophilicity compared to Ti. The SBPTi-rhSLPI enhanced 7-day protein retention on the surface. While Ti promoted higher cell proliferation, the modified groups demonstrated superior cell adhesion and mineralization. Specifically, SBPTi-rhSLPI showed the highest cytoplasmic spreading, adhesion-related gene expression (Itg$\alpha$1, Itg$\alpha$2, Itg$\alpha$5, and Itg$\beta$1), and mineralization. Additionally, rhSLPI-coated groups effectively reduced the adhesion of both S. aureus and E. coli. In conclusion, combining SLA modification, argon plasma treatment, and rhSLPI coating provides enhanced effects. This combined approach significantly enhances osteoblast adhesion and mineralization while possessing antibacterial potential, which could be a promising strategy to improve implant success rates. Full article

The role of Fusobacterium nucleatum (F. nucleatum) in regulating exosome-mediated communication between oral squamous cell carcinoma (OSCC) cells and lymphatic endothelial cells (LECs) remains poorly understood. Here, we confirmed the presence of F. nucleatum in OSCC tissues and showed that it induced inflammation- and vesicle-associated transcriptional changes in OSCC cells. Exosomes were isolated by differential ultracentrifugation, and quantitative analyses demonstrated that F. nucleatum stimulation increased exosome yield from OSCC cells. In vitro, pretreatment of LECs with exosomes derived from F. nucleatum-stimulated OSCC cells (Fn-Exo) enhanced OSCC cell adhesion to LEC monolayers. Fn-Exo upregulated intercellular adhesion molecule 1 (ICAM1) expression in LECs, and ICAM1 blockade partially reduced Fn-Exo-induced OSCC cell adhesion to LECs. Fn-Exo increased intracellular reactive oxygen species (ROS) accumulation and promoted NF-κB p65 phosphorylation and nuclear translocation in LECs. N-acetyl-L-cysteine (NAC) attenuated Fn-Exo-induced ROS accumulation and NF-κB activation, and both NAC and the NF-κB inhibitor BAY 11-7082 reduced ICAM1 upregulation and partially attenuated the enhanced adhesion of OSCC cells to Fn-Exo-treated LECs. These pharmacological inhibition experiments support the involvement of ROS/NF-κB/ICAM1 signaling in the Fn-Exo-induced pro-adhesive phenotype. Collectively, these findings indicate that F. nucleatum is associated with increased exosome yield from OSCC cells and that Fn-Exo enhances the adhesive interaction between OSCC cells and LECs. Full article

Matrix metalloproteinases (MMPs) have long been recognized as key mediators of tumor invasion and metastasis due to their capacity to degrade extracellular matrix components. However, clinical failure of broad-spectrum MMP inhibitors has revealed a more complex and context-dependent role for these proteases in cancer. Among them, macrophage metalloelastase, MMP-12, has emerged as a particularly intriguing enzyme with both tumor-promoting and tumor-suppressive functions. Predominantly expressed by tumor-associated macrophages, MMP-12 occupies a unique position at the interface of proteolysis, inflammation, and immune regulation within the tumor microenvironment. Accumulating evidence from experimental models and clinical studies demonstrates that MMP-12 can exert potent anti-tumorigenic effects, primarily through inhibition of angiogenesis. Mechanistically, MMP-12 generates angiostatin and other anti-angiogenic fragments, suppresses vascular endothelial growth factor signaling, and reduces tumor vascularization, thereby limiting tumor growth and metastatic expansion. In several cancer types, including lung, colorectal, and hepatocellular carcinoma, elevated MMP-12 expression has been associated with reduced tumor progression and improved patient outcomes. Conversely, MMP-12 can also promote tumor progression through extracellular matrix remodeling, facilitation of invasion, and modulation of inflammatory pathways, particularly in environments characterized by chronic inflammation or immunosuppressive macrophage phenotypes. These seemingly contradictory roles are governed by multiple context-dependent factors, including macrophage polarization, tumor type, disease stage, and microenvironmental cues such as hypoxia and cytokine signaling. In this review, we comprehensively examine the molecular regulation, functional mechanisms, and clinical relevance of MMP-12 in cancer. We highlight the dualistic nature of MMP-12 activity and discuss its implications for therapeutic strategies, emphasizing the need for selective and context-aware targeting approaches rather than broad inhibition of MMP activity. Full article

Poly(acrylic acid)-based superabsorbent polymer (PAA-SAP) rapidly absorbs water and swells during pipeline transport in mine water-based inhibitor fluids, increasing flow resistance and potentially causing blockage. To improve aqueous structural stability, PAA-SAP beads were coated with poly(vinyl alcohol) (PVA) by rotary spraying and hot-air curing, with borax introduced to regulate the coating structure. The effects of PVA concentration, coating thickness, temperature, and hydrodynamic disturbance were evaluated using stability tests, scanning electron microscope (SEM), energy-dispersive X-ray spectrometer (EDS), fourier transform infrared (FTIR), X-ray photoelectron spectroscopy (XPS), dry-film swelling, and mass-loss analyses. A 10% PVA formulation showed favorable film-forming and processing performance. Increasing coating thickness prolonged structural retention, whereas higher temperature and stronger disturbance accelerated hydration and failure. At 0.30 mm coating thickness and 2.5 m·s⁻¹ laboratory hydrodynamic disturbance parameter, the borax-modified PVA coating failed after approximately 16 min, compared with 10 and 12 min for PVA and PVA/poly(vinylpyrrolidone) (PVP) coatings, respectively. Boron incorporation and possible boron–oxygen interactions restricted chain mobility and improved coating compactness and stability. A power-law model based on 46 datasets showed good interpolation performance (Coefficient of determination (R²) = 0.9421; Mean Absolute Percentage Error (MAPE) = 5.44%). Failure involved swelling, gelation, network weakening, cracking, and chain dissolution, with core swelling potentially promoting crack propagation. These findings support coating-parameter selection and subsequent mine-scale pipeline validation. Full article

High-grade osteosarcoma presents a significant clinical challenge due to unpredictable therapeutic responses and aggressive progression. This study aimed to identify the critical molecular pathways driving chemotherapy resistance and aggressive phenotypes in osteosarcoma patients. Through transcriptomic and bioinformatic analyses, we identified cholesterol biosynthesis as a key upregulated metabolic pathway in poor chemotherapy responders, where squalene epoxidase (SQLE) emerged as an exploratory candidate hub gene whose elevated expression significantly correlates with shortened survival in the TCGA cohort. We validated these findings by administering terbinafine, a known SQLE inhibitor. In highly chemoresistant SaOS-2 cells exhibiting the highest baseline SQLE expression, terbinafine synergistically sensitized cells to doxorubicin by driving cell death partly through apoptosis, as confirmed by caspase inhibition. The combination also promoted ferroptosis, indicated by elevated ROS and MDA along with decreased FSP1 and GPX4 expression. Furthermore, the co-treatment effectively suppressed clonogenic potential, induced G2/M phase cell cycle arrest, and inhibited metastatic progression. These effects were mediated by the modulation of cell proliferation, metastasis, and survival genes through the coordinated regulation of the PI3K/AKT/mTOR, ERK, and JNK signaling cascades. Together, these results highlight the therapeutic potential of targeting the SQLE pathway to overcome doxorubicin resistance and suppress aggressive progression in high-grade osteosarcoma. Full article

Sterile alpha and Toll/interleukin-1 receptor motif-containing protein 1 (SARM1) is an inducible NAD-consuming enzyme and execution factor in axon degeneration. Rapid ATP collapse after SARM1 activation, however, is not fully explained by NAD depletion alone. We used SARM1-overexpressing HEK293 cells and the cell-permeant activator CZ-48 to examine SARM1-induced non-apoptotic cell death, termed sarmoptosis. CZ-48 induced cell death that was suppressed by HSP90/70-annotated ATP-competitive compounds, especially geldanamycin and VER-155008 (VER), without reducing SARM1 abundance. VER preserved NAD and ATP during SARM1 activation but failed to rescue FK866-mediated NAD starvation, thereby distinguishing CZ-48/SARM1-driven cytotoxicity from generic NAD depletion. In cell-free assays, purified SARM1 reduced ATP levels; this effect was enhanced by SARM1’s activator NMN and attenuated by its pharmacological inhibitors, although the in vitro activity was modest and the reaction products remain to be identified. ATPase-related perturbations, including thapsigargin and bafilomycin A1, also protected cells from CZ-48-induced death, further supporting a central role for ATP collapse in sarmoptosis. iTRAQ proteomics, MitoSOX Red staining, and DiOC6(3) staining revealed that CZ-48 treatment was associated with mitochondrial and metabolic remodeling, mitochondrial ROS accumulation, and mitochondrial depolarization, all of which were mitigated by VER. Collectively, these findings support a convergent ATP-collapse model in which SARM1 activation promotes NAD depletion, directly consumes ATP, and is associated with mitochondrial dysfunction that may amplify ATP-production failure. Full article

Background/Objectives: Chronic metabolic inflammation is associated with pro-inflammatory macrophage activation and mitochondrial dysfunction. Semaglutide, a widely used GLP-1 receptor agonist, has been reported to possess systemic anti-inflammatory properties, but its action on human macrophages, especially in the context of mitochondrial regulation, remains poorly understood. The aim of the study was to evaluate the direct effect of semaglutide on macrophage polarization and to investigate the roles of cAMP signaling and mitochondrial regulation in this process. Methods: THP-1 and U-937 monocytic cell lines were differentiated into macrophages and polarized into the M1-like phenotype using LPS/IFN-γ. Cells were treated with 100 nM semaglutide in the presence or absence of the adenylyl cyclase inhibitor SQ22536. Intracellular cAMP levels, mRNA expression of macrophage markers and key regulators of mitochondrial biogenesis (SIRT1 and PGC-1α), and levels of pro- and anti-inflammatory cytokines were determined. The COX-1/SDH-A and mtDNA/nDNA ratios were analyzed as markers of mitochondrial biogenesis. Results: Semaglutide induced cAMP accumulation in M0- and M1-like macrophages derived from both cell lines. This response was significantly attenuated by GLP-1R antagonist exendin(9–39), supporting the presence of functional GLP-1R signaling. Semaglutide supplementation during inflammatory polarization resulted in reduced levels of pro-inflammatory markers (CD80/CD86, TNF-α, IL-6) and increased expression of M2-associated genes CD206 and CD163 and secretion of the anti-inflammatory cytokine IL-10. Semaglutide also increased SIRT1 and PGC-1α expression, the COX-1/SDH-A ratio, and the mtDNA/nDNA ratio, suggesting activation of processes associated with mitochondrial biogenesis. All of the effects of semaglutide described above were attenuated by SQ22536, supporting an important contribution of cAMP signaling to these responses. Conclusions: Semaglutide acts directly on human monocytic cell line-derived macrophages, attenuating the M1-like program and promoting a shift toward a less inflammatory phenotype. These effects strongly depend on cAMP signaling and are accompanied by increased expression of SIRT1 and PGC-1α and mitochondrial changes consistent with enhanced biogenesis. Full article

Melon (Cucumis melo L.) is a globally significant horticultural crop whose fruit quality and postharvest shelf life are profoundly influenced by oxidative stress. Abscisic acid (ABA)-responsive element binding factors (ABFs), which represent the Group A subfamily of the basic leucine zipper (bZIP) transcription factor family, serve as pivotal components in the ABA signaling pathway. These factors play essential roles in regulating plant responses to abiotic stress as well as fruit development and maturation processes. In this study, a total of nine CmABF gene family members (CmABF1–CmABF9) were successfully identified within the melon genome using genome-wide identification techniques. Bioinformatic analysis indicated that all CmABF proteins contain a conserved bZIP domain. Physicochemical property analysis revealed that most of these proteins are unstable hydrophilic proteins and all are localized to the cell nucleus. Phylogenetic analysis categorized the CmABF family into three distinct evolutionary branches (Groups A, B, and C), exhibiting high conservation with homologous genes in Arabidopsis thaliana, Solanum tuberosum, and other species. Promoter analysis demonstrated that CmABF genes are rich in hormone-responsive elements (such as abscisic acid-responsive element (ABRE) and gibberellin-responsive element (GARE)) and stress-responsive elements (such as MYB binding sites (MBS) and anaerobic-response element (ARE)). To investigate their responses to oxidative stress and ABA signaling, we analyzed the expression patterns of these genes in melon fruit at 0, 7, 14, 21, 28, and 35 days of postharvest storage under ozone (O₃, an oxidative stressor), exogenous abscisic acid (ABA), and the ABA synthesis inhibitor nordihydroguaiaretic acid (NDGA) using RNA-seq and qRT-PCR. The results showed that ozone treatment significantly induced the up-regulation of CmABF9 while inhibiting the early expression of CmABF2 and CmABF4. ABA treatment generally promoted the transcription of family members during the late stages of storage (35 d). NDGA treatment suppressed the expression of CmABF2 and CmABF4 during the early storage stage (7 d), while markedly increasing their expression levels at later storage stages (28 d and 35 d), suggesting a compensatory feedback response under endogenous ABA deficiency. Furthermore, protein–protein interaction predictions indicated potential close interactions between CmABF proteins and SnRK2 protein kinases. This study provides a theoretical basis for elucidating the molecular mechanisms of the CmABF family in regulating postharvest oxidative stress in melon and provides candidate gene resources for molecular breeding aimed at enhancing resistance and extending the shelf life of melon fruit. Full article

Articular cartilage exists under hypoxic conditions, where hypoxia-inducible factor (HIF)-1α plays a critical role in maintaining its homeostasis. In osteoarthritis (OA), however, this hypoxic environment is disrupted, and decreased HIF-1α expression contributes to disease progression. HIF-prolyl hydroxylase (HIF-PH) inhibitors stabilize HIF-1α and are clinically used to treat renal anemia; therefore, they may also exert therapeutic effects in OA through the same mechanism. However, their effects on articular cartilage remain unclear. In this study, we investigated the effects of Roxadustat, a HIF-PH inhibitor, both in vitro using rat chondrocytes and in vivo using a monosodium iodoacetate (MIA)-induced rat OA model. Roxadustat showed no cytotoxicity and significantly increased the protein expression of HIF-1α, SRY-box transcription factor 9 (SOX9), and Aggrecan in monolayer cultures. In three-dimensional spheroid cultures, Roxadustat enhanced Safranin O staining and extracellular matrix production and significantly upregulated SOX9 and ACAN mRNA expression. Furthermore, intra-articular administration of Roxadustat in the MIA-induced OA model suppressed cartilage degeneration and significantly reduced the Modified Mankin score. These findings demonstrate that Roxadustat promotes anabolic responses in chondrocytes through stabilization of HIF-1α and suppresses cartilage degeneration in OA. Intra-articular administration of HIF-PH inhibitors may represent a novel disease-modifying therapeutic strategy for OA. Full article

Non-small-cell lung cancer (NSCLC) treatment is hampered by its complex pathogenesis and high heterogeneity. N6-methyladenosine (m⁶A) represents the most common post-transcriptional modification regulating RNA stability and function in eukaryotes. This methylation is catalyzed by methyltransferase complexes, with METTL14 being the core catalytic subunit. Abnormal expression of lncRNA MSTRG.292666.16 is related to poor prognosis of NSCLC. However, the mechanism by which it regulates NSCLC progression through m⁶A modification remains unclear. We employed cell function experiments, molecular mechanism analysis, RNA interaction experiments, and a nude mouse tumor model to explore the roles of METTL14-mediated MSTRG.292666.16 m⁶A modification in NSCLC and the potential MAPK signaling pathway involved. METTL14 was significantly upregulated in NSCLC cell lines and promoted m⁶A modification of MSTRG.292666.16 by forming a stable association with it. METTL14 knockdown significantly inhibited the viability, migration and invasion of A549 cells and promoted apoptosis, whereas MSTRG.292666.16 overexpression reversed these effects. Mechanistically, METTL14 upregulated the expression of MSTRG.292666.16 through m⁶A modification, thereby activating the MAPK pathway (manifested as elevated levels of MAPK8IP3 and p-ERK1/2). The use of a selective p38 MAPK inhibitor SB203580 stimulated the tumor-suppressive effect of METTL14 knockdown, whereas the activator U-46619 reversed it. In vivo experiments confirmed that METTL14 knockdown significantly inhibited tumor growth, whereas MSTRG.292666.16 overexpression partially restored the malignant phenotype of the tumor, which was associated with MAPK pathway activation. This study revealed that METTL14-dependent m⁶A modification of MSTRG.292666.16 may act as an upstream driver to activate the MAPK cascade and facilitate NSCLC progression. These findings clarify a key epitranscriptomic regulatory mechanism driving NSCLC development and offer preliminary molecular clues for exploring potential therapeutic targets in subsequent clinical NSCLC research. Full article

Background: Immune checkpoint inhibitors have improved outcomes in metastatic clear-cell renal cell carcinoma (mRCC), yet clinically applicable tissue biomarkers remain limited. Growth differentiation factor-15 (GDF-15) promotes tumour immune evasion and has emerged as a potential therapeutic target in immuno-oncology. We evaluated the prognostic significance of tumour GDF-15 expression in patients with intermediate-risk clear-cell mRCC treated with second-line nivolumab. Methods: Forty-six patients with intermediate-risk clear-cell mRCC who received nivolumab after one line of tyrosine kinase inhibitor therapy were retrospectively evaluated. Tumour GDF-15 expression was assessed by immunohistochemistry and classified as low (0–1+) or high (2–3+). Objective response rate (ORR), progression-free survival (PFS), overall survival (OS), and the development of cancer-associated cachexia were compared between expression groups. Results: High tumour GDF-15 expression was observed in 23 patients (50%). ORR was significantly higher in the low-expression group than in the high-expression group (57% vs. 26%, p = 0.036). Low tumour GDF-15 expression was associated with significantly longer PFS (24.5 vs. 7.5 months; HR 0.38, 95% CI 0.18–0.80; p = 0.009) and OS (28.6 vs. 12.6 months; HR 0.43, 95% CI 0.19–0.98; p = 0.041). The association with OS remained significant after adjustment for age. The frequency of cancer-associated cachexia did not differ according to tumour GDF-15 expression (43% vs. 35%, p = 0.546). Conclusions: Low tumour GDF-15 expression was associated with better objective response and longer progression-free and overall survival in patients with intermediate-risk metastatic clear-cell renal cell carcinoma treated with second-line nivolumab, with the association with overall survival remaining significant after adjustment for age. Tumour GDF-15 represents a promising tissue biomarker for prognostic risk stratification and warrants validation in larger prospective studies. Full article

Understanding the mechanisms of metastasis is one of the most pressing issues in cancer therapy. Metastasis-associated in colon cancer 1 (MACC1) is an important biomarker and functional driver of tumor progression and metastasis. However, the molecular mechanisms underlying its activity remain incompletely understood. Here, we demonstrate that MACC1 acts as an important adaptor protein that promotes hyperactivation of receptor tyrosine kinase (RTK) signaling pathways in colorectal cancer (CRC) cells. Based on mass spectrometry-based interactomics, we identified key MACC1 interactors, including GRB2, SHP2, SHC1, and STAT5B, that preferentially associate with tyrosine-phosphorylated residues Y365, Y379, and Y789. Site-directed mutagenesis of Y379 and Y789 reduced MACC1-induced migration, proliferation, and ERK phosphorylation. Using digital Western blotting (DigiWest), we observed a broad MACC1-dependent hyperactivation of downstream signaling effectors, including MEK, ERK, β-catenin, SRC, FAK, CREB, and VASP. Targeting MACC1-induced signaling with clinically relevant inhibitors effectively reversed MACC1-driven clonogenicity. Our findings support a role for MACC1 in promoting hyperactivation of RTK-associated signaling and reveal pharmacological vulnerabilities of potential relevance to metastasis-prone cancers characterized by elevated MACC1 expression. Full article

Clear cell renal cell carcinoma (ccRCC) is a highly immune-evasive malignancy that exhibits limited and often transient responses to immune checkpoint inhibitors (ICIs) and remains a major challenge for emerging cellular immunotherapies, including chimeric antigen receptor (CAR)-T cells. A defining feature of ccRCC, largely driven by von Hippel–Lindau (VHL) deficiency, is persistent activation of the transforming growth factor-β1 (TGF-β1) and hypoxia-inducible factor (HIF) signaling network. Acting as a central immunometabolic regulatory axis, TGF-β1/HIF promotes angiogenesis, metabolic reprogramming, epigenetic dysregulation, and immune escape through coordinated induction of immunosuppressive mediators, including PD-L1, VEGF, and CTLA-4, resulting in impaired T-cell infiltration, functional exhaustion, and resistance to immunotherapy. Preclinical studies have demonstrated that pharmacologic-dose Seleno-L-methionine (SLM) and its active metabolite, methylseleninic acid (MSA), suppress TGF-β1 and both HIF-1α and HIF-2α, leading to downregulation of multiple downstream immunosuppressive pathways at pharmacologically achievable, non-toxic concentrations. In addition to enhancing the antitumor activity of chemotherapy and VEGF-targeted agents, accumulating evidence suggests that SLM exerts broad immunologic, metabolic, and epigenetic effects that may overcome key mechanisms of therapeutic resistance. This review synthesizes current mechanistic and translational evidence supporting the repurposing of SLM as a first-in-class pleiotropic immunomodulatory agent. Using ccRCC as a model of TGF-β1/HIF-driven immune resistance, we discuss how simultaneous targeting of this central regulatory axis may restore immune surveillance, improve T-cell fitness and trafficking, enhance responses to ICIs and CAR-T cell therapy, and provide a mechanistically rational strategy for the treatment of advanced solid tumors. Full article

The gut microbiota can influence tumor immunity and treatment responses through microbial metabolism, intestinal barrier regulation, and immune–inflammatory signaling, but whether exercise engages these mechanisms through the muscle–gut axis remains uncertain. This review integrates evidence from exercise physiology, microbial metabolism, and tumor immunology to examine how exercise-associated host signals may reshape the intestinal ecological niche and microbial function. Three candidate muscle–gut axes are proposed: the myokine–enteroendocrine–substrate delivery–short-chain fatty acid (SCFA) axis, the exercise-associated lactate–microbial cross-feeding–propionate axis, and the muscle-derived endocrine signaling–intestinal epithelial repair–hypoxic niche axis. Separate studies support exercise-associated IL-6/GLP-1/PYY regulation and gastrointestinal transit, lactate entry into the intestinal lumen and lactate-associated microbial remodeling, Veillonella atypica-mediated propionate production, and irisin/apelin-related epithelial repair. Together, these pathways may influence microbial metabolism, barrier homeostasis, and immune–tumor interactions. However, tumor-related links remain incomplete, and none has been validated as a complete causal chain in a single tumor-bearing exercise model. Relatively complete preclinical evidence comes from mouse melanoma, where endurance exercise enhanced microbial folate-dependent one-carbon metabolism and formate output, with microbiota-derived formate promoting CD8⁺ T-cell antitumor activity and immune checkpoint inhibitor efficacy. Regular exercise with an appropriate load and adequate recovery may support microbial and intestinal barrier homeostasis, whereas excessive or prolonged exercise with inadequate recovery may impair barrier integrity. Human evidence remains limited and largely associative and does not establish microbiota-mediated improvements in tumor immunity or treatment responses. These candidate axes therefore require causal validation in tumor-bearing exercise models and prospective human studies. Full article

Kaposi’s sarcoma-associated herpesvirus (KSHV) is an oncogenic gammaherpesvirus that causes Kaposi’s sarcoma (KS), an endothelial cell-derived malignancy that primarily affects immunocompromised individuals. During lytic reactivation, KSHV expresses viral proteins that promote viral replication and modulate host signaling pathways. Here, we identified the calcium-activated chloride channel ANO1 (TMEM16A) as a previously unrecognized host factor induced by the KSHV lytic protein vGPCR. RNA sequencing, RT-qPCR, and immunofluorescence analyses demonstrated robust ANO1 upregulation in vGPCR-expressing endothelial cells and during KSHV lytic reactivation. siRNA-mediated depletion of vGPCR significantly reduced ANO1 expression, demonstrating that vGPCR contributes to ANO1 induction during infection. Functionally, ANO1 knockdown sensitized vGPCR-expressing endothelial cells to caspase-dependent apoptosis under serum-starved conditions, which was rescued by the pan-caspase inhibitor Z-VAD-FMK. In reactivated iSLK.BAC16 cells, genetic or pharmacological inhibition of ANO1 increased late apoptosis, enhanced KSHV lytic gene expression, and promoted infectious virion production. Together, these findings identify ANO1 as a vGPCR-regulated host factor that promotes cell survival and modulates KSHV lytic replication, highlighting ANO1 signaling as a potential therapeutic target in KSHV-associated disease. Full article