Critical Signaling Research Articles

The Spillover Effects of Cryptocurrency Trading Ban and Social Media on Domestic Fintech

In 2021, China implemented a sweeping cryptocurrency trading ban, significantly disrupting the cryptocurrency market. However, the impact of this regulatory action on domestic fintech companies has largely been overlooked. This paper investigates two key research questions: first, whether the 2021 Chinese cryptocurrency trading ban had spillover effects on the domestic fintech sector, and second, whether crypto-related social media sentiment influenced fintech companies differently before and after the ban. To address these questions, we employ a GARCH(1,1) model to analyze market volatility and trends. Additionally, we train a fine-tuned BERT model to enhance the accuracy of social media sentiment analysis. Our findings reveal that the cryptocurrency ban not only directly impacted the crypto market but also led to significant negative spillover effects on fintech firms. Following the ban, social media sentimentespecially concerning Bitcoinbecame a dominant factor, with fintech companies serving as a proxy for exposure to the digital finance sector. Positive sentiment surrounding cryptocurrencies served as a critical signal for speculative interest in fintech stocks post-ban.

The small GTPase MRAS is a broken switch

Intense research on founding members of the RAS superfamily has defined our understanding of these critical signalling proteins, leading to the premise that small GTPases function as molecular switches dependent on differential nucleotide loading. The closest homologs of H/K/NRAS are the three-member RRAS family, and interest in the MRAS GTPase as a regulator of MAPK activity has recently intensified. We show here that MRAS does not function as a classical switch and is unable to exchange GDP-to-GTP in solution or when tethered to a lipid bilayer. The exchange defect is unaffected by inclusion of the GEF SOS1 and is conserved in a distal ortholog from nematodes. Synthetic activating mutations widely used to study the function of MRAS in a presumed GTP-loaded state do not increase exchange, but instead drive effector binding due to sampling of an activated conformation in the GDP-loaded state. This includes nucleation of the SHOC2-PP1Cα holophosphatase complex. Acquisition of NMR spectra from isotopically labeled MRAS in live cells validated the GTPase remains fully GDP-loaded, even a supposed activated mutant. These data show that RAS GTPases, including those most similar to KRAS, have disparate biochemical activities and challenge current dogma on MRAS, suggesting previous data may need reinterpretation.

Single-cell multi-omics deciphers hepatocyte dedifferentiation and illuminates maintenance strategies.

Due to the similarity to human hepatocytes, porcine hepatocytes play an important role in hepatic research and drug evaluation. However, once hepatocytes were cultured in vitro, it was often prone to dedifferentiate, resulting in the loss of their characteristic features and normal functions, which impede their application in liver transplantation and hepatotoxic drugs evaluation. Up to now, this process has yet to be thoroughly investigated from the single-cell resolution and multi-omics perspective. In this study, we utilized 10× multiome technology to dissect the heterogeneity of porcine hepatocytes at different time points (Days 0, 1, 3, 5 and 7) during dedifferentiation. We comprehensively investigated cell heterogeneity, cellular dynamics, signalling pathways, potential gene targets, enhancer-driven gene regulatory networks, cell-cell communications of these cells and the conservation of mechanisms across species. We found that a series of critical signalling pathways driven by ERK, PI3K, Src and TGF-β were activated during this process, especially in the early stage of dedifferentiation. Based on these discoveries, we constructed a chemical combination targeting these pathways, which effectively inhibited the dedifferentiation of porcine hepatocytes in vitro. To validate the effectiveness of this combination, we transplanted such treated hepatocytes into FRGN mice, and the results demonstrated that these cells could effectively repopulate the liver and improve the survival of mice.

Interrogation of the Tumor Microenvironment by Nanoparticles.

The tumor microenvironment (TME) plays a pivotal role in cancer progression by fostering intricate multicellular crosstalk among cancer cells, stromal cells, and immune cells. This review explores the emerging paradigm of utilizing nanoparticles to disrupt this crosstalk within the TME as a therapeutic strategy. Nanoparticles are engineered with precise physicochemical properties to target specific cell types and deliver therapeutic payloads, thereby inhibiting critical signaling pathways involved in tumor growth, invasion, and metastasis. The mechanisms involved include modulation of the immune response, interference with growth factor signaling, and induction of programmed cell death in cancer cells. Challenges such as biocompatibility, efficient delivery, and potential development of resistance are discussed alongside promising advancements in nanoparticle design. Moving forward, integration of nanoparticle-based therapies with existing treatment modalities holds great potential for enhancing therapeutic efficacy and personalized medicine in cancer therapy.

Nitric oxide release as a defense mechanism in marine microalgae against microplastic-induced stress.

Nitric oxide (NO) has garnered significant attention as a critical regulatory factor and signaling molecule in plant growth. However, the effects of microplastic pollution on the release of NO by algae have not been reported. Thus, in this study, the release of NO by Skeletonema costatum and Gymnodinium sp. when exposed to different concentrations (5-50 mg/L) of polystyrene microplastics (PS, 0.1 μm) after a 15-day cultivation period was investigated. PS microplastics negatively impacted the photosynthetic processes of microalgae through several mechanisms, such as aggregation and adsorption, consequently affecting their physiological state. This physiological damage increased reactive oxygen species (ROS), which subsequently inhibited algal growth. However, the activity of nitrate reductase increased, and the released NO was able to scavenge ROS, alleviating oxidative stress and providing microalgae with a temporary adaptive advantage. This adaptability was only observed from day 3 to 7; beyond that period, microplastics continued to inflict irreversible toxicity on the microalgae. Notably, the toxicity of PS microplastics was less pronounced in S. costatum compared with Gymnodinium sp. Overall, these findings reveal that marine microalgae can release NO, mitigating the short-term toxic effects of microplastic pollution.

Redox modification of m6A demethylase SlALKBH2 in tomato regulates fruit ripening.

Hydrogen peroxide (H2O2) functions as a critical signalling molecule in controlling multiple biological processes. How H2O2 signalling integrates with other regulatory pathways such as epigenetic modification to coordinately regulate plant development remains elusive. Here we report that SlALKBH2, an m6A demethylase required for normal ripening of tomato fruit, is sensitive to oxidative modification by H2O2, which leads to the formation of homodimers mediated by intermolecular disulfide bonds, and Cys39 serves as a key site in this process. The oxidation of SlALKBH2 promotes protein stability and facilitates its function towards the target transcripts including the pivotal ripening gene SlDML2 encoding a DNA demethylase. Furthermore, we demonstrate that the thioredoxin reductase SlNTRC interacts with SlALKBH2 and catalyses its reduction, thereby modulating m6A levels and fruit ripening. Our study establishes a molecular link between H2O2 and m6A methylation and highlights the importance of redox regulation of m6A modifiers in controlling fruit ripening.

Resveratrol ameliorates postoperative cognitive dysfunction in aged mice by regulating microglial polarization through CX3CL1/CX3CR1 signaling axis.

Postoperative cognitive dysfunction (POCD) is a common cognitive challenge faced by older adults. One of the key contributors to the development of POCD is neuroinflammation induced by microglia. Resveratrol has emerged as a promising candidate for the prevention of cognitive decline. Previous studies have demonstrated its potential in alleviating cognitive deterioration, yielding encouraging results. Nonetheless, the mechanism of resveratrol improving cognitive function remains unclear. Therefore, we assessed the effect of resveratrol in both aged POCD model mice and BV2 cells on CX3CL1/CX3CR1 axis, a critical signaling pathway mediating microglial activity. Both in vitro and in vivo experiments have revealed that pre-administration of resveratrol not only mitigates cognitive deficits but also significantly reduces the levels of inflammatory cytokines. Additionally, it enhanced the expression of SIRT1 and CX3CR1 within the hippocampal region. We also evaluated the impact of resveratrol on CX3CR1 siRNA transfected BV2 cells. Delete of CX3CR1 reversed the preventive role of resveratrol. Our findings implied that resveratrol might inhibit microglial activation and improve cognition by mediating CX3CL1/CX3CR1 signaling.

Osterix mRNA Enrichment in Small Extracellular Vesicles Derived From Osteogenically Induced ADSCs: A Promoter of Osteogenic Differentiation in BMSCs.

Osteogenic differentiation of bone marrow stem cells (BMSCs) is essential for bone tissue regeneration and repair. However, this process is often hindered by an unstable differentiation influenced by local microenvironmental factors. While small extracellular vesicles (sEVs) derived from osteogenically induced adipose mesenchymal stem cells (ADSCs) reportedly can promote osteogenic differentiation of BMSCs, the underlying molecular mechanisms remain incompletely understood. In this study, we investigated the mRNA expression profile of ADSC-sEVs+ and explored the role of specific mRNAs in the osteogenic differentiation of BMSCs. We first validated the osteogenic induction activity of ADSC-sEVs+ through both invitro and invivo experiments. Using reverse transcription polymerase chain reaction, we compared mRNA expression between ADSC-sEVs+ and ADSC-sEVs and further assessed the impact of specific mRNAs on the differentiation of BMSCs through a series of invitro experiments. One of our key findings was that osterix mRNA was highly enriched in ADSC-sEVs+, which significantly enhanced alkaline phosphatase staining and upregulated downstream osteoblastic markers in BMSCs. Both overexpression and knockdown experiments confirmed that osterix mRNA is a critical signalling molecule that facilitates the differentiation of BMSCs into osteoblasts through ADSC-sEVs+. This finding expands our understanding of the molecular mechanisms underlying the osteogenic differentiation of BMSCs and offers a promising strategy for targeted osteoblastic differentiation in clinical applications.

Targeting protein modification: a new direction for immunotherapy of pancreatic cancer.

Post-translational modifications (PTMs) alter protein conformation by covalently attaching functional groups to substrates, influencing their biological activity, mechanisms of action, and functional performance. PTMs and their interactions are essential to many critical signal transduction processes, including tumor transformation, cancer progression, and metastasis in pancreatic cancer. Additionally, advancements in tumor immunotherapy indicate that PTMs are essential in immune cell activation, transport, and energy metabolism. This study aimed to investigate the effects of different PTMs on immunotherapy for pancreatic cancer, providing new perspectives and suggesting directions for future research.

Exploring seasonal dynamics of sea spray aerosol bioactivity: Insights into molecular effects on human bronchial epithelial cells.

Sea spray aerosol (SSA) is a complex mixture of natural substances that can be inhaled by coastal residents. Previous studies have suggested that SSA may have positive effects on human health, but the molecular mechanisms and the factors influencing these effects are poorly understood. In this study, we exposed human bronchial epithelial cells (BEAS-2B) to natural SSA samples, collected monthly using quartz microfiber filters mounted on tripods within 15m of the waterline, with air drawn through pumps, throughout a one-year period at the Ostend coast, Belgium, and measured cellular gene expression changes using RNA sequencing. To simulate environmentally relevant exposure conditions, SSA extracts were applied at scaled doses equivalent to human alveolar exposure levels (multiplicative factors M = 10, 20, 40, and 80). We found that SSA exposure influenced the expression of genes involved in critical signaling pathways: mTOR, PI3K, Akt, and NF-κB were downregulated, while AMPK was upregulated. Downregulation of mTOR, PI3K, Akt, and NF-κB potentially indicates a protective response against tumor-promoting and inflammatory signals, whereas upregulation of AMPK may confer a beneficial effect on metabolic regulation. The number and direction of differentially expressed genes (DEGs) varied depending on the SSA sampling time and correlated with the phytoplankton density and chemical diversity of the SSA samples. Our results suggest that SSA contains bioactive compounds that may originate from marine algae and modulate cellular processes related to human health. We provide novel insights into the molecular effects of SSA exposure and highlight its potential as a source of natural therapeutics. To our knowledge, this is the first study to expose human lung cells to natural SSA at environmentally relevant levels, presenting a pioneering exploration of seasonal variations in exposure effects.

Signaling pathway regulators in preimplantation embryos.

Embryonic development during the preimplantation stages is highly sensitive and critically dependent on the reception of signaling cues. The precise coordination of diverse pathways and signaling factors is essential for successful embryonic progression. Even minor disruptions in these factors can result in physiological dysfunction, fetal malformations, or embryonic arrest. This issue is particularly evident in assisted reproductive technologies, such as in vitro fertilization, where embryonic arrest is frequently observed. A detailed understanding of these pathways enhances insight into the fundamental mechanisms underlying cellular processes and their contributions to embryonic development. The significance of elucidating signaling pathways and their regulatory factors in preimplantation development cannot be overstated. The application of this knowledge in laboratory settings has the potential to support strategies for modeling developmental stages and diseases, drug screening, therapeutic discovery, and reducing embryonic arrest. Furthermore, using various factors, small molecules, and pharmacological agents can enable the development or optimization of culture media for enhanced embryonic viability. While numerous pathways influence preimplantation development, this study examines several critical signaling pathways in this contex.

A bacterial membrane-disrupting protein stimulates animal metamorphosis.

This research describes a mechanism wherein a bacterium prompts the metamorphic development of an animal from larva to juvenile form by injecting a protein that disrupts membranes in the larval cilia. Specifically, results show that a bacterial contractile injection system and the protein effector it injects form pores in larval cilia, influencing critical signaling pathways like mitogen-activated protein kinase and calcium flux, ultimately driving animal metamorphosis. This discovery sheds light on how a bacterial protein effector exerts its activity through membrane disruption, a phenomenon observed in various bacterial toxins affecting cellular functions, and elicits a developmental response. This work reveals a potential strategy used by marine organisms to respond to microbial cues, which could inform efforts in coral reef restoration and biofouling prevention. The study's insights into metamorphosis-associated contractile structures' delivery of protein effectors to specific anatomical locations highlight prospects for future biomedical and environmental applications.

Unraveling non-coding RNAs in breast cancer: mechanistic insights and therapeutic potential.

Breast cancer remains a leading global health challenge requiring innovative, therapeutic strategies to improve patient outcomes. This review explores the pivotal roles of non-coding RNAs (ncRNAs), including long non-coding RNA, micro RNA, and circular RNA, in breast cancer biology. We highlight how these molecules regulate critical signaling pathways, influence tumor microenvironments, and contribute to treatment resistance. Our findings underscore the potential of ncRNAs as biomarkers for early diagnosis and as treatment targets for personalized treatment strategies. To pave the way for innovative cancer management approaches, we investigate the complex interactions of ncRNAs and their impact on tumor progression. This comprehensive review enhances our understanding of breast cancer biologywhile emphasizing the translational significance of ncRNA research in developing effective treatment strategies. Additional research and clinical studies are required to confirm the diagnostic and medicinal value of ncRNAs in breast cancer. Investigating the complex networks of ncRNA interactions and their links to other biological pathways can lead to the discovery of new treatment targets. Furthermore, leveraging advanced technologies, such as machine learning and multi-omics methods, will be critical in improving our understanding of ncRNAs biomarkers and translating these insights into impactful clinical applications.

Signal-Centric Framework Based on Probability of Detection for Real-Time Reliability of Concrete Damage Inspection

Passive nondestructive testing (NDT) methods allow one to detect damage by the energies emitted from the internal processes. While the test conditions can be controlled and repeatable, obtained data are random, and the probability of detection (PoD) is affected. However, in concrete with complex fracture behavior, factors such as signal attenuation, sensor-damage distance, and test configuration influence the reliability of the test. The conventional practice of proceeding without assessing credibility prevents the ability to determine whether a configuration modification is required, necessitating reassessment. The main objective of this study is to develop a signal-centric framework to enhance the real-time reliability of inspection by investigating the PoD of acoustic emission (AE), a widely used passive NDT method for the real-time monitoring of structures. This study’s purpose is to evaluate the mechanical processes and the passive signal responses, emphasizing the detectability of cracking in concrete with two PoD approaches, namely, amplitude- and energy-based PoDs. Additionally, critical signal signatures, namely, signal-to-noise ratio (SNR) and frequency, were pinpointed for their direct influence on the detectability of the crack. With the outcomes obtained, a novel framework, which aims to provide an adaptive evaluation of the PoD of the technique, was suggested to achieve the desired quality in the damage detection of structures.

TGFβ signaling sensitizes MEKi-resistant human melanoma to targeted therapy-induced apoptosis

The TGFβ signaling pathway is known for its pleiotropic functions in a plethora of biological processes. In melanoma, TGFβ signaling promotes invasiveness and metastasis formation. However, its involvement in the response to therapy is controversial. While several studies have linked TGFβ signaling to elevated resistance to targeted therapy in melanoma, separate findings have indicated a favorable treatment response through TGFβ-mediated increase of cell death. We now found that the outcome of TGFβ signaling in the context of targeted therapy is dose dependent. Unlike low doses, high levels of TGFβ signal activation induce apoptosis upon simultaneous MAPK pathway inhibition, even in targeted therapy resistant melanoma cell lines. Using transcriptomic analyses, combined with genomic target identification of the critical TGFβ signaling effector SMAD4, we demonstrate that parallel activation of TGFβ signaling and MAPK pathway inhibition causes a complete switch of TGFβ target genes from promoting pro-invasive processes to fueling pro-apoptotic pathways. Investigations of underlying mechanisms identified a novel apoptosis-inducing gene signature. Functional validation of signature members highlighted a central role of the pro-apoptotic BCL2 family member BCL2L11 (BIM) in mediating apoptosis in this condition. Using a modified, synthetic version of the TGFB1 mRNA for intra-tumoral injections, we additionally showcase a potential therapeutic application of this treatment combination.

Dysregulated miRNA Expression and Androgen Receptor Loss in Racially Distinct Triple-Negative Breast Cancer.

Androgen receptor (AR)-negative triple-negative breast cancer (TNBC), often termed quadruple-negative breast cancer (QNBC), disproportionately impacts women of African descent, leading to poorer overall survival (OS). MiRNAs regulate the expression of gene drivers involved in critical signaling pathways in TNBC, such as the AR gene, and their expression varies across races and breast cancer subtypes. This study investigates whether differentially expressed miRNAs influence AR transcription, potentially contributing to the observed disparities between African American (AA) and European American (EA) QNBC patients. Race-annotated TNBC samples (n = 129) were analyzed for AR expression status and revealed the prevalence of QNBC in AA patients compared to EA (76.6% vs. 57.7%) and a significant association of AR loss with poor survival among AAs. The Cancer Genome Atlas (TCGA) RNA-seq data showed that AAs with TNBC (n = 32) had lower AR mRNA levels than EAs (n = 67). Among TCGA patients in the AR-low group, AAs had significantly poorer OS than EAs. In our cohort, 46 miRNAs exhibited differential expression between AAs and EAs with QNBC. Ten of these miRNAs (miR-1185-5p, miR-1305, miR-3161, miR-3690, miR-494-3p, miR-509-3-5p, miR-619-3p, miR-628-3p, miR-873-5p, and miR-877-5p) were predicted to target the AR gene/signaling. The loss of AR expression is linked to poorer prognoses in AA women. The understanding of the specific miRNAs involved and their regulatory mechanisms on AR expression could provide valuable insights into why AA women are more prone to QNBC.

Napabucasin-loaded PLGA nanoparticles trigger anti-HCC immune responses by metabolic reprogramming of tumor-associated macrophages

BackgroundJAK/STAT3 is one of the critical signaling pathways involved in the occurrence and development of hepatocellular carcinoma (HCC). BBI608 (Napabucasin), as a novel small molecule inhibitor of STAT3, has shown previously excellent anti-HCC effects in vitro and in mouse models. However, low bioavailability, high cytotoxicity and other shortcomings limit its clinical application. In this study, PLGA was selected to prepare Napabucasin PLGA nanoparticles (NPs) by solvent evaporation method, overcoming these limitations and improving the passive targeting effect that nanoparticle mediated. Base on this, we systematically evaluated the anti-HCC effect of Napabucasin-PLGA NPs and explored the underlying mechanisms.MethodsNapabucasin-PLGA NPs were prepared by solvent evaporation method. CCK-8 assay, Annexin V/PI double staining, RT-qPCR, colony formation assay, and Western blotting were performed to evaluate the anti-HCC effect of Napabucasin-PLGA NPs in vitro. Proliferation assay and migration assay were used to detect the effects of Napabucasin-PLGA NPs-treated HCC-TAMs on tumor biological characteristics of HCC cells. Flow cytometry was used to detect anti-HCC immune responses induced by Napabucasin-PLGA NPs in vivo.ResultsOur results demonstrated that Napabucasin-PLGA NPs could improve the bioavailability of Napabucasin and enhance Napabucasin-mediated the anti-HCC effects in vitro and in vivo with no significant drug toxicity. In addition to the direct inhibitory effects on the tumor biological characteristics of HCC cells, Napabucasin-PLGA NPs could promote the polarization of macrophages from tumor-promoting M2-type to anti-tumor M1-type, improving the tumor immune microenvironment and augmenting T cell-mediated anti-tumor responses. The underlining mechanisms showed Napabucasin-PLGA NPs suppressed the STAT3/FAO signaling axis in HCC-induced tumor-associated macrophages (TAMs).ConclusionsThese findings demonstrated Napabucasin-PLGA NPs is a potential therapeutic candidate for HCC, and provided a new theoretical and experimental basis for further development and clinical application of Napabucasin.

Nuclear microRNA 9 mediates G-quadruplex formation and 3D genome organization during TGF-β-induced transcription

The dynamics of three-dimensional (3D) genome organization are essential to transcriptional regulation. While enhancers regulate spatiotemporal gene expression, chromatin looping is a means for enhancer-promoter interactions yielding cell-type-specific gene expression. Further, non-canonical DNA secondary structures, such as G-quadruplexes (G4s), are related to increased gene expression. However, the role of G4s in promoter-distal regulatory elements, such as super-enhancers (SE), and in chromatin looping has remained elusive. Here we show that mature microRNA 9 (miR-9) is enriched at promoters and SE of genes that are inducible by transforming growth factor beta 1 (TGFB1) signaling. Moreover, we find that miR-9 is required for formation of G4s, promoter-super-enhancer looping and broad domains of the euchromatin histone mark H3K4me3 at TGFB1-responsive genes. Our study places miR-9 in the same functional context with G4s and promoter-enhancer interactions during 3D genome organization and transcriptional activation induced by TGFB1 signaling, a critical signaling pathway in cancer and fibrosis.

SPAG5 is a potential therapeutic target affecting proliferation, apoptosis, and invasion of esophageal cancer cells

BackgroundSperm-associated antigen 5 (SPAG5) is a mitotic spindle protein crucial for coordinating the separation of sister chromatids into daughter cells. Increasing evidence suggests that SPAG5 is overexpressed in various malignancies, functioning as an oncogene. However, research specifically examining SPAG5 in esophageal cancer remains limited.MethodsIn this research, we leveraged bioinformatics techniques to evaluate the expression and prognostic significance of SPAG5 in a variety of cancer types. We conducted Gene Set Enrichment Analysis (GSEA) to elucidate the relationship between SPAG5 and cancer characteristics. Additionally, we investigated the correlation between SPAG5 expression and immune cell infiltration utilizing the TIMER2.0 platform. The TIDE platform was used to assess the impact of SPAG5 on the effectiveness of immunotherapy and to screen for potential therapeutic drugs. We employed qRT-PCR and immunohistochemistry staining to ascertain the expression of SPAG5 in esophageal cancer tissue. Through cellular functional experiments, we examined the influence of SPAG5 expression on the proliferation, apoptosis, invasion, and migration of esophageal cancer cells. The Pathscan Stress Signaling Antibody Array was utilized to probe the potential molecular mechanisms of SPAG5.ResultsSPAG5 exhibits high levels of expression in various cancers, encompassing esophageal cancer, and its presence indicates an unfavorable prognosis. SPAG5 is primarily enriched in pathways associated with cellular proliferation and demonstrates a correlation with immune gene expression as well as the infiltration of immune cells. Suppression of SPAG5 expression in esophageal cancer cells not only inhibits cell proliferation, but also attenuates cell invasion and migration while inducing cellular apoptosis. The depletion of SPAG5 results in a decline in the levels of critical signaling proteins.ConclusionSPAG5 plays a pivotal role in esophageal cancer cell proliferation, apoptosis, and metastasis within the tumor microenvironment, making it a promising therapeutic target.

Cytotoxic effects of bee venom-loaded ZIF-8 nanoparticles on thyroid cancer cells: a promising strategy for targeted therapy.

Thyroid cancer continues to be a notable health issue, requiring the creation of novel treatment methods to enhance patient results. The objective of this study is to investigate the potential of utilizing bee venom (BV)-loaded zeolitic imidazolate framework-8 (ZIF-8) nanoparticles as a novel strategy for specifically targeting and treating medullary thyroid cancer cells. Due to their wide surface area and configurable pore size, ZIF-8 nanoparticles are ideal for drug delivery. Bee venom's cytotoxic capabilities are used in ZIF-8 nanoparticles to target thyroid cancer cells more effectively. ZIF-8 nanoparticles containing bee venom were tested on TT medullary thyroid cancer cell lines. The effects of these nanoparticles on cell viability, proliferation, and apoptosis were investigated. IC50 value at 24h for BV-ZIF-8 nanoparticles in TT medullary thyroid carcinoma cells was determined to be 17.19µg/mL, while the IC50 value at 48h was determined to be 16.39µg/mL. It has been demonstrated that nanoparticle treatment upregulates the Bax and caspase-3 genes while downregulating the Bcl-2, CCND1, and CDK4 genes. Additionally, it was observed that oxidative stress was triggered in the nanoparticle-treated group. Furthermore, an examination of its mechanisms was conducted, with a specific emphasis on the modulation of critical signaling pathways that are implicated in the progression of cancer. In thyroid cancer cells, ZIF-8 nanoparticles infused with bee venom promote programmed cell death and impair key biological processes.