International Journal of Biological Macromolecules

Characterization of a polysaccharide with antioxidant and anti-cervical cancer potentials from the corn silk cultivated in Jilin province

Corn silk polysaccharides (CSPs) were extracted from the corn silk cultivated in Jilin province, China, where is one of the golden corn belts worldwide. Three fractions (CSP-1, CSP-2 and CSP-3) were obtained by DEAE-52 cellulose and the former two fractions were further purified by Sephadex G-150 column chromatography to obtain CSP-S-1 and CSP-S-2. The molecular weights of CSP-S-1 and CSP-S-2 were calculated to be 586 kDa and 813 kDa, respectively. CSP-S-1 was composed of galactose, arabinose, xylose and rhamnose at a molar ratio of 4.16:1.00:1.01:6.32 and CSP-S-2 was composed of galactose, arabinose, glucose and rhamnose at a molar ratio of 8.71:3.58:0.169:1.00. CSP-S-2 outperformed CSP-S-1 in scavenging DPPH, ABTS and hydroxyl radicals, and significantly inhibited the proliferation of HeLa cells. IR and NMR analysis indicated that CSP-S-2 was pyranose. CSP-S-2 consisted of 1 → 4 and 1 → 6 linkages and exhibited a triple helix configuration. In summary, CSP-S-2 possesses high potential to be developed as a novel antioxidant and anti-cervical cancer agent.

Carboxylesterase-activatable multi-in-one nanoplatform for near-infrared fluorescence imaging guided chemo/photodynamic/sonodynamic therapy toward cervical cancer

Traditional tumor treatment faces great challenge owning to inherent drawbacks. Activatable prodrugs with multi-modality therapeutic capacity are highly desired. In this consideration, a responsiveness-released multi-in-one nanoplatform, PLGA-PEG@HC, toward cervical cancer therapy was innovatively developed. Among the nanoplatform, HC was constructed by incorporating chlorambucil, a classic chemotherapy drug into a near-infrared photo- and sono-sensitizer, HCH via ester linker, which can be specifically hydrolyzed by carboxylesterase (CES). HC is scarcely fluorescent and toxic due to the caging of HCH and chlorambucil, thus achieving low background signal and minimal side effects. However, once selectively hydrolyzed by tumor enriched CES, ester bond will be broken. Consequently, HCH and chlorambucil are released so as to achieve near-infrared fluorescence imaging and synergistic photodynamic/sonodynamic/chemo therapy. PLGA-PEG packaging ensures the biocompatibility of HC. The as-obtained nanoplatform, with diameter of 97 nm, achieves tumor targeting capacity via EPR. In vitro and in vivo applications have demonstrated that PLGA-PEG@HC can accumulate in tumor tissues, exhibit CES-activatable near-infrared fluorescence imaging and efficient tumor suppression capacity. Compared with the reported combinational therapy materials which are complex in compositions, PLGA-PEG@HC is simple in formulation but demonstrates near-infrared fluorescence traced and considerable therapy efficacy toward tumors, which may accelerate the clinical translation.

Atranorin from lichens act as potential inhibitor for cervical tumor proteins TGFbeta and kinase enzyme CDK4/CyclinD3: An anti-cancer intervention therapy

In the present study a potential anticancer compound atranorin was identified and isolated from the foliose lichen Heterodermia boryi. The study also evaluated the pharmacological potential of the foliose lichens Sticta weigelii and Heterodermia boryi against cervical cancer. Qualitative analysis of phytochemicals revealed the presence of alkaloids, flavonoids, phenolics, terpenoids and tannin compounds in both lichens. Saponins and glycosides are present only in S. weigelii. The presence of atranorin in H. boryi was confirmed by HPTLC, and its structure was elucidated by

Self-amplifying mRNA nanovaccine encoding GM-CSF-fused HPV16 E7 enhances immunogenicity and therapeutic efficacy against cervical cancer

Cervical cancer, driven by the malignant transformation of keratinocytes via the human papillomavirus (HPV) E7 oncoprotein, remains a significant global health challenge. In this study, we developed an alphavirus-based self-amplifying mRNA (saRNA) vaccine encoding either a genetically engineered HPV16 E7 gene or a fusion of granulocyte-macrophage colony-stimulating factor (GM-CSF) with HPV16 E7, both encapsulated in self-assembling liposome-protamine-RNA (LPR) nanoparticles. SaRNA represents a promising vaccine platform due to its intrinsic ability to amplify and prolong antigen expression, offering a substantial advantage over conventional mRNA approaches. Intramuscular administration of LPR-saRNA-GM-CSF-E7 in mice triggered robust innate immune responses and activated antigen-presenting cells in the draining lymph nodes, leading to enhanced T-cell effector functions. The LPR-saRNA-GM-CSF-E7 nanovaccine more effectively reprogrammed the tumor microenvironment by reducing immunosuppressive cell populations and increasing Th1 cytokine expression compared to LPR-saRNA-E7. Importantly, in vivo cytotoxic T lymphocyte (CTL) assays demonstrated that LPR-saRNA-GM-CSF-E7 vaccination elicited potent E7-specific CD8

Magnetic casein-CaFe2O4 nanohybrid carrier conjugated with progesterone for enhanced cytotoxicity of citrus peel derived hesperidin drug towards breast and ovarian cancer

A novel progesterone-receptor targeted nanohybrid carrier based delivery of hesperidin was investigated in the present work. Casein‑calcium ferrite nanohybrid carrier was synthesized using desolvation followed by ionic-gelation. The citrus peel extracted hesperidin drug (CHD) was encapsulated in the carrier via pH based coacervation, after which the targeting ligand progesterone was conjugated through activate ester procedure. The carrier formulation was characterized using techniques like XRD, FTIR, SEM, VSM and DLS. The bioactive components in CHD were analyzed using HPLC. Taguchi optimization gave a maximum of 89.54% hesperidin encapsulation in the carrier. Incorporation of superparamagnetic calcium ferrite nanoparticles resulted in improved drug encapsulation and magnetic induced drug delivery. The carrier exhibited a stimuli-responsive drug release behavior, with good stability at physiological pH (7.4) and a higher release under acidic pH (5.4 and 1.2) favoring anticancer applications. The drug release followed Fickian diffusion mechanism as predicted by different kinetic models. Cell viability assay on L929 fibroblast cells verified the biocompatibility of the formulation. The specific recognition and targeted chemotherapy rendered by the progesterone-conjugated carrier enhanced the cytotoxicity of CHD against SKOV-3 ovarian and MDA-MB-231 breast cancer cells, resulting in a significant 30-fold reduction in the (Half-maximal inhibitory concentration) IC

The combination of a small molecular prodrug and hyaluronic acid-tocopherol assembly as a nano-agent for the synergistic therapy of cervical cancer

The therapeutic efficacy of the anticancer drug chlorambucil (Cbl) is severely hampered by its poor water solubility and serious off-target toxicity. To address these issues and to further improve therapeutic outcomes, we developed an innovative nano-agent that combines an activatable prodrug with an active tumor-targeting delivery system for the simultaneous imaging and treatment of cervical cancer. Guided by what we call a "two-birds-with-one-stone" concept, we first synthesized a carboxylesterase-activated near-infrared fluorescent prodrug capable of photo-sonodynamic therapy, that can generate abundant reactive oxygen species so as to enhance antitumor efficacy. This prodrug was subsequently encapsulated into an assembly formed from hyaluronic acid and α-tocopherol succinate (TOS), endowing the final nano-agent with improved water-solubility, extended blood retention half-life, CD44-mediated tumor-targeting ability, and TOS-derived cytotoxicity. This compact nano-agent served as both a sensitive near-infrared carboxylesterase indicator (with a detection limit of 0.057 U/mL) and a potent antitumor drug, achieving both 76 % inhibition of HeLa cell growth upon laser/ultrasound irradiation and significant tumor suppression in vivo. Unlike most reported nano-formulations that rely on complex multi-component systems for synergistic therapy, our design was built upon the repeated application of a "two-birds-with-one-stone" philosophy, resulting in a simplified yet effective nano-agent with great clinical potential.

Immunochromatographic assay for rapid detection of SIGLEC15 to evaluate its therapeutic potential in cervical cancer

SIGLEC15 is a novel immunosuppressive transmembrane protein promotes cancer development. However, the role of SIGLEC15 in cervical cancer remains poorly understood until now. In this study, we identified that the expression of SIGLEC15 was significantly increased in cervical cancer cells and tissues, and it was closely related to the metastasis of cervical cancer (70.6 %). Several anti-SIGLEC15 mAbs (named 6E3, 2B7, 3G2, 4F6, 4C4, 2F6) were prepared and identified, the titers were from 1:64000 to 1:128000. The results of IFA, IPMA, and IHC revealed that 6E3 (exhibiting a Kaff of 281,200,000 L/mol) had the capability to bind to cervical cancer cells and tissues. Then, the quantum dot nanoparticles probe (QDs-6E3) was synthesized and optimized. Moreover, the QDs based Immunochromatography Assay (QDs-ICA) method for the detection of SIGLEC15 was developed. After several evaluations, SIGLEC15 proved detectable at concentrations as low as 3 ng/mL within 4 min, demonstrating no cross-reactivity. The QDs-ICA exhibited a specificity of 96.7 % and a sensitivity of 96 %. The QDs-ICA for detecting SIGLEC15 is of great significance for the non-invasive screening of patients in clinical trials and the accurate evaluation of the therapeutic effect of this target in cervical cancer.

Development of palmatine chloride-loaded chitosan nanoparticles for enhanced and safe cervical cancer therapy

Cervical cancer remains a significant global health issue, highlighting the need for novel drug delivery strategies to improve the efficacy of anticancer agents against it. In this study, palmatine chloride-loaded chitosan nanoparticles (PC-CSNPs) were developed via ionic gelation as biocompatible nanocarriers for cervical cancer therapy. The physical properties of PCNPs were characterized using SEM, FTIR, XRD, and DLS, revealing a spherical morphology and average particle sizes of 55 nm (chitosan) and 58 nm (PCNPs).FTIR and XRD confirmed successful drug encapsulation and an amorphous structure of the nanoparticles. Drug loading and encapsulation efficiencies increased in a dose-dependent manner, with maximum encapsulation (80.2 %) at 40 μg and enhanced retention at acidic pH. PCNPs exhibited notable antioxidant activity, with peak efficacy at 100 μg/mL. Antimicrobial activity was most pronounced against Streptococcus pneumoniae (1.9 mm zone at 75 μg/mL concentration).In vitro anticancer studies on HeLa cells revealed strong cytotoxicity, with an IC

Exploring the mechanism by which BXSD decoction treats cervical cancer through the combination of network pharmacology and molecular docking analysis: Molecular mechanism of AKT1 and CASP3 protein

As a traditional Chinese medicine prescription, BXSD has attracted extensive attention for its potential in cancer treatment. The proliferation and metastasis of tumor cells are regulated by a variety of signaling pathways, among which AKT1 and CASP3 proteins play an important role in the occurrence and development of cancer. The aim of the study was to explore the potential of BXSD decoction in the treatment of cancer through the molecular mechanism of AKT1 and CASP3 proteins, and to reveal its mechanism in the treatment of cancer, especially cervical cancer, through the combination of network pharmacology and molecular docking analysis. We used network pharmacology to screen the chemical constituents of BXSD and its associated targets, and identified key targets by constructing protein-protein interaction (PPI) networks. On this basis, the component disease target network was constructed, and GO biological function and KEGG pathway enrichment analysis were performed. The binding ability of BXSD to AKT1 and CASP3 was confirmed by molecular docking analysis. Finally, the effects of BXSD on the proliferation, migration and invasion of cervical cancer cells were verified in vivo and in vitro. The results of network pharmacological analysis showed that several chemical components of BXSD were associated with AKT1 and CASP3, which were identified as key targets by PPI network analysis. Molecular docking results showed that BXSD was stably bound to AKT1 and CASP3. Experimental verification showed that BXSD significantly inhibited the proliferation, migration and invasion of HeLa cells, and this effect was related to the downregulation of AKT1 and CASP3. Therefore, BXSD decoction can inhibit the growth and metastasis of cancer cells by regulating the expression and function of AKT1 and CASP3.

Deciphering the mechanism of baicalein in cervical cancer via bioinformatics, machine learning and computational simulations: PIM1 and CDK2 are key target proteins

Cervical cancer is one of the leading causes of death among women worldwide. Current treatments are limited by chemoresistance and chemotherapeutic agents' adverse effects, prompting the search for better therapeutic alternatives. Baicalein, a natural compound with potent antitumor activity and low toxicity, has drawn significant attention. However, the precise mechanisms of baicalein against cervical cancer remain to be fully elucidated. In this study, bioinformatics and machine learning algorithms predicted six potential core targets of baicalein against cervical cancer. Molecular docking and molecular dynamics simulations were employed to further validate these targets, with a focus on assessing their binding affinity and stability. The molecular docking results demonstrated that five of the core targets exhibited significant binding affinity with baicalein. Notably, PIM1 and CDK2 showed stable binding conformations in molecular dynamics simulations. GO and KEGG enrichment analyses indicated baicalein might regulate cell cycle progression via histone kinase - mediated phosphorylation modifications. Thus, baicalein likely suppresses cervical cancer cells' abnormal proliferation by inhibiting PIM1 and CDK2 activity, inducing cell cycle arrest.

METTL3-mediated m6A modification of PAK6 drives cervical cancer progression through activating MAPK14

N6-methyladenosine (m6A) is the most prevalent epitranscriptomic modification in mammalian mRNA. Recent studies have revealed that m6A modification is involved in cervical cancer (CC) pathogenesis, yet the precise mechanisms remain largely unexplored. In this study, we identified DDX5 as a binding partner of the methyltransferase METTL3 in CC cells, demonstrating that DDX5 interacts with METTL3 to regulate global m6A levels. Additionally, METTL3-mediated m6A modification stabilizes PAK6 mRNA through recognition by the m6A reader IGF2BP1. Gain- and loss-of-function studies revealed that PAK6 enhances the proliferation, migration and invasion capability of CC cells by phosphorylating MAPK14 at the Ser56 residue. In vivo experiments further corroborated that METTL3 promotes CC growth and metastasis by upregulating PAK6. Notably, a positive correlation between METTL3 and PAK6 expression is observed in clinical specimens of CC. Collectively, our findings highlight the critical role of METTL3/PAK6 axis in driving CC progression, offering potential therapeutic targets for patients with CC.

The fucoidan delivery system enhanced the anti-cervical cancer effect of caffeic acid

Cervical cancer remains one of the leading causes of mortality among women, and immunotherapy targeting the cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) pathway holds promise for its treatment. This study has developed nanoparticles based on fucoidan (Fu/CA NPs), successfully loading them with caffeic acid (CA) for application in cervical cancer therapy. In vitro experiments revealed that Fu/CA NPs significantly inhibited the proliferation of cervical cancer HeLa cells (by 65.73 ± 4.06 %) and induced apoptosis through the accumulation of reactive oxygen species and mitochondrial damage. Furthermore, treatment with Fu/CA NPs activated the cGAS-STING pathway, attributed to the cytoplasmic release of mitochondrial DNA (mtDNA) and the induction of DNA double-strand breaks (dsDNA) by Fu/CA NPs. In vivo results confirmed that Fu/CA NPs suppressed solid tumor growth (by 67.8 %), with even more pronounced antitumor effects observed when combined with cisplatin (96.5 %), a phenomenon also associated with the activation of the cGAS-STING pathway. Excitingly, the combination of Fu/CA NPs and cisplatin alleviated cisplatin-induced nephrotoxicity, as indicated by a decrease in blood urea nitrogen (BUN) by 53.27 % and serum creatinine (SCr) by 74.93 %. In summary, our research presents a potential therapeutic avenue for cervical cancer treatment, particularly highlighting the synergistic benefits of combining Fu/CA NPs with cisplatin.

Mitochondrial oxidative stress related LncRNA predict cervical cancer prognosis and immunotherapy response: Molecular structure and protein interaction of ribosomal protein L34

The purpose of this study was to investigate the predictive value of mitochondrial oxidative stress-related LncRNA in cancer prognosis and immunotherapy response, and to further analyze the molecular structure of ribosomal protein L34 and its interaction mechanism with the protein. We screened lncrnas associated with mitochondrial oxidative stress, evaluated their expression patterns in different cancer types, and analyzed the three-dimensional structure of ribosomal protein L34 and its interaction network with other proteins. In this study, public databases were used to screen out lncrnas associated with mitochondrial oxidative stress. Bioinformatic analysis, including gene expression profile analysis, survival analysis and functional enrichment analysis, was used to evaluate the expression patterns of these lncrnas in different cancer types and their relationship with prognosis. The interacting proteins of ribosomal protein L34 were identified by proteomic techniques. The three-dimensional structure of ribosomal protein L34 and its binding mode with interacting proteins were studied by molecular docking and dynamic simulation methods. The results showed that the screened lncrnas showed significant expression differences in multiple cancer types and were closely related to the survival rate of patients. The three-dimensional structure of ribosomal protein L34 reveals key amino acid residues and binding sites for its interactions with specific proteins. Functional enrichment analysis showed that these lncrnas may affect the development of cancer through regulating oxidative stress response, cell cycle and apoptosis. The interaction network of ribosomal protein L34 reveals its central role in protein synthesis and cellular stress response.

Inhibition of human cervical cancer development through p53-dependent pathways induced by the specified triple helical β-glucan

This study demonstrates that the purified β-glucan (LNT) with a triple helix and relatively narrow molecular weight distribution, extracted and purified from artificially cultured Lentinus edodes, showed a significant cervical cancer inhibition with little cytotoxicity against normal cells in vitro and in vivo. From the in vitro data, the potential mechanism of anti-cervical cancer was preliminarily revealed as follows: LNT was firstly recognized by the human cervical cancer cell line of Hela and induced cell proliferation inhibition through p21 and apoptosis via a mitochondrion-dependent pathway by targeting the tumor suppressor of p53, indicated by an increase in reactive oxygen species (ROS) generation and a loss of mitochondrial membrane potential (Δψ

Extracellular vesicles targeting tumor microenvironment in ovarian cancer

Ovarian cancer (OC) is a prevalent neoplastic condition affecting women. Extracellular vesicles (EVs), nano-sized membrane vesicles, are secreted by various cells in both physiological and pathological states. The profound interplay between EVs and the tumor microenvironment (TME) in ovarian cancer is crucial. In this review, we explores the pivotal role of EVs in facilitating intercellular communication between cancer cells and the TME, emphasizing the potential of EVs as promising diagnostic markers and innovative therapeutic targets for ovarian cancer. The comprehensive analysis outlines the specific mechanisms by which EVs engage in communication with the constituents of the TME, including the modulation of tumor growth through EVs carrying matrix metalloproteinases (MMPs) and EV-mediated inhibition of angiogenesis, among other factors. Additionally, the we discuss the potential clinical applications of EVs that target the TME in ovarian cancer, encompassing the establishment of novel treatment strategies and the identification of novel biomarkers for early detection and prognosis. Finally, this review identifies novel strategies for therapeutic interventions, such as utilizing EVs as carriers for drug delivery and targeting specific EV-mediated signaling pathways. In summary, this manuscript offers valuable insights into the role of EVs in ovarian cancer and highlights the significance of comprehending intercellular communication in the realm of cancer biology.

A novel strategy to enhance inhibition of Hela cervical cancer by combining Lentinus β-glucan and autophagic flux blockage

Lentinus β-D-glucan (LNT), derived from artificially cultured mushrooms of Lentinus edodes, shows an important yet incompletely understood biological functions in cancer. In this work, the chemical structure of the refined LNT comprising a β-D-(1, 6)-branched β-D-(1,3)-glucan was further clarified via 1D- and 2D-NMR with high resolution, and its drug resistance resulted from autophagy in human cervical cancer (CC) Hela cells besides its anti-cancer function were revealed in vitro and in vivo. In detail, LNT destroyed cellular homeostasis by significantly increasing the intracellular Ca

Albumin nanoparticles with tunable ultraviolet-to-red autofluorescence for label-free cell imaging and selective biosensing of copper ion

Early and simple detection of aberrant cooper metabolism in diseases with neurological-manifestations and several other conditions, including cancer, becomes an urgent necessity. Instrumental methods used today are limited to high-cost equipment and reagents and demand highly qualified personnel. In this work, we report easy-to-use and cost-effective nano-sized sensors for the selective and quantitative detection of copper ion based on fluorescence quenching. Glutaraldehyde cross-linked albumin nanoparticles with tunable ultraviolet-to-red autofluorescence emissions are developed as dual-agents for sensing and imaging. These albumin nanoparticles show great selectivity towards copper ion when tested against a selection of biochemical components and other metal ions, and a limit of detection as low as 1.9 μM, relevant for sensing in clinical diagnosis, was determined. In addition, a lack of toxicity and good cellular uptake were observed and the ultraviolet-to-red intrinsic fluorescence of the albumin nanoparticles was preserved when tested in vitro on NIH:OVCAR3 cell line. Preliminary studies confirm the albumin nanoparticles' ability to detect Cu

Preparation and physicochemical properties of cisplatin and doxorubicin encapsulated by niosome alginate nanocarrier for cancer therapy

Alginate (AL), in the form of a hydrogel, is extensively used in drug delivery. In the current study, an optimum formulation of alginate-coated niosome-based nanocarriers for co-delivery of doxorubicin (Dox) and cisplatin (Cis) was obtained for the treatment of breast and ovarian cancers in an attempt to decrease drug doses and overcome multidrug resistance. The physiochemical characteristics of uncoated niosomes containing Cis and Dox (Nio-Cis-Dox) compared to alginate-coated niosomes formulation (Nio-Cis-Dox-AL). The three-level Box-Behnken method was examined to optimize the particle size, polydispersity index, entrapment efficacy (%), and percent drug release of nanocarriers. Nio-Cis-Dox-AL showed appropriate encapsulation efficiencies of 65.54 ± 1.25 % and 80.65 ± 1.80 % for Cis and Dox, respectively. Maximum drug release decreased from niosomes in case coated by alginate. Also, the zeta potential value of Nio-Cis-Dox nanocarriers decreased after coating with alginate. In vitro cellular and molecular experiments were performed to investigate the anticancer activity of Nio-Cis-Dox and Nio-Cis-Dox-AL. MTT assay showed the IC

Preparation of polypeptide-metal complexes-coated Hosenkoside A and its inhibitory effect in cervical cancer

We reported the anti-cervical cancer effect of proprietary saponin content from seeds of Impatiens balsamina L., Hosenkoside A. Our study found that Hosenkoside A significantly promotes cell apoptosis and cell cycle arrest after administration, exhibiting anti-tumor effects. Then the transcriptome sequencing results after administration showed that Hosenkoside A had a significant inhibitory effect on Histone deacetylase 3 (HDAC3). After sufficient administration time, the inhibition of HDAC3 expression level leads to a significant decrease in lysine acetylation at histone 3 sites 4 and 9, blocking the activation of Signal transducer and activator of transcription 3 (STAT3) and achieving anti-tumor effects. In addition, we encapsulated Hosenkoside A into polypeptide metal complexes (PMC) to form slow-release spheres. This material breaks down in the tumor environment, not only does it solve the problem of low drug solubility, but it also achieves targeted sustained-release drug delivery. Under the same concentration of stimulation, the PMC complex group showed better anti-tumor effects in both in vitro and in vivo experiments.

Micro-interdigitated electrodes genosensor based on Au-deposited nanoparticles for early detection of cervical cancer

Genosensor-based electrodes mediated with nanoparticles (NPs) have tremendously developed in medical diagnosis. Herein, we report a facile, rapid, low cost and highly sensitive biosensing strategy for early detection of HPV 18 using gold-nanoparticles (AuNPs) deposited on micro-IDEs. This study represents surface charge transduction of micro-interdigitated electrodes (micro-IDE) alumina insulated with silica, independent and mini genosensor modified with colloidal gold NPs (AuNPs), and determination of gene hybridization for early detection of cervical cancer. The surface of AuNPs deposited micro-IDE functionalized with optimized 3-aminopropyl-triethoxysilane (APTES) followed by hybridization with deoxyribonucleic acid (DNA) virus to develop DNA genosensor. The results of ssDNA hybridization with the ssDNA target of human papillomavirus (HPV) 18 have affirmed that micro-IDE functionalized with colloidal AuNPs resulted in the lowest detection at 0.529 aM. Based on coefficient regression, micro-IDE functionalized with AuNPs produces better results in the sensitivity test (R

Directed evolution of proteoglycan-modifying enzymes: Functional applications in cervical cancer therapy

The study investigates the therapeutic potential of enzyme variations EP-22, DS-13, and SM-47 in cervical cancer treatment using HeLa and SiHa cell lines, focusing on their effects on cell viability, migration, and molecular targets. The MTT assay findings also show that at a concentration of 50 μg/mL, EP-22 has an IC50 value of 35 % for HeLa cells and 28 % for SiHa cells, a significant dose effect (p < 0.01). EP-22 was not less potent at a lower working concentration of 25 μg/mL and could reduce HeLa cell viability to 78 %. In this case, there were significant changes in the anti-migratory effect, as evidenced by 45 % inhibition of SiHa cell migration and a 12 % wound closure rate compared with 54 % in the untreated cells. The obtained densitometric analysis indicated that in EP-22 treated HeLa cells, syndecan-1 and perlecan protein levels were reduced by approximately 65 % and 57 %, respectively, while the MMP-2 and MMP-9 levels were reduced to about 50 % and 45 %, respectively. Annexin V staining also highlighted a 40 % enhancement in early apoptosis and 25 % in late apoptosis in EP-22 handled cells. These data suggest the potential of EP-22 and its derivatives as therapeutic molecules in cervical cancer treatment, reducing HeLa proliferation by 35 % and SiHa by 28 %, inhibiting SiHa migration by 45 %, and affecting molecular targets involved in adhesion and invasiveness. Future studies must elucidate the effectiveness of in vivo experiments and how these findings were obtained. At 50 μg/mL, EP-22 reduced HeLa and SiHa cell viability by 35 % and 28 %, respectively, with significant dose-dependent effects (p < 0.01). At 25 μg/mL, EP-22 maintained potency, reducing HeLa cell viability to 78 %. EP-22 inhibited SiHa cell migration by 45 % and reduced wound closure rates to 12 % compared to 54 % in untreated cells. This work uses the HeLa and SiHa cell lines to examine the therapeutic potential of enzyme variation EP-22 in cervical cancer. EP-22 showed significant anti-cancer effects at 50 μg/mL doses, reducing cell viability at lower concentrations and achieving an IC50 of 35 % for HeLa cells and 28 % for SiHa cells. It is worth mentioning that EP-22 considerably reduced levels of essential proteins: syndecan-1 (65 %), perlecan (57 %), MMP-2 (50 %), and MMP-9 (45 %), in addition to inhibiting SiHa cell migration by 45 %. Furthermore, annexin V staining showed that treated cells exhibited a 40 % increase in early apoptosis and a 25 % increase in late apoptosis.

Polysaccharides from Pyracantha fortuneana and its biological activity

This study used response surface methodology to determine the optimal conditions for extraction of polysaccharides from Pyracantha. fortuneana (PSPF), and studied the mechanism of PSPF-inducing apoptosis in human ovarian carcinoma Skov3 cells. Response surface methodology (RSM) were adopted to extract PSPF. The maximum value of polysaccharide yield was obtained under these optimal conditions. PSPF had good potential as an antioxidant. Exposure of cells to PSPF resulted in cytotoxicity through the induction of apoptosis, and the reactive oxygen species were increased, mitochondrial membrane potential decreased, DNA damage (detected as γ- H2AX and RAD51 foci) was observed in Skov3 cells. In addition, PSPF could induce apoptosis of cancer cells. Therefore, PSPF should be explored as novel potential antioxidants and an anti-tumor drug in a clinical setting.

Methotrexate-conjugated chitosan-grafted pH- and thermo-responsive magnetic nanoparticles for targeted therapy of ovarian cancer

Here, methotrexate (MTX)-conjugated multifunctional nanoparticles (NPs) were engineered based on chitosan (CS) for targeted delivery of erlotinib (ETB). First, CS was modified with sodium dodecyl sulfate and maleic anhydride to prepare a polymerizable organo-soluble precursor. N-Isopropylacrylamide (NIPAAm) and itaconic acid (IA) as thermo- and pH-responsive monomers were grafted onto CS by free radical polymerization. Subsequently, magnetic nanoparticles (MNPs) ferrofluid with prepared CS copolymer (CSC) was produced via an inclusion complex between carboxylic acid groups of CSC and MNPs. Finally, MTX was conjugated to amino groups of CS based on the structural similarity of MTX with folic acid as targeting ligand. The prepared MTX-CSC@MNPs were physiochemically characterized by different techniques, including FT-IR,

Folate-chitosan nanoparticles loaded with an apolar acetogenin inhibiting the proliferation of cervical cancer cells

The folk medicine Annona muricata is used widely against cancer. Three acetogenins AMPE I, AMPE II and AMPE III were isolated from the leaves of A. muricata and were identified as epomuricenin-A, epomuricenin-B and epomusenin-B respectively. FACS NPs were prepared and characterised by FTIR, particle size, zeta potential (ZP), TGA, SEM and TEM analysis. The average particle size and ZP of the encapsulated chitosan NPs and folic acid conjugated chitosan NP were 52 nm and 71 nm, 32.75 mV and 42.85 mV respectively. Among the acetogenins epomuricenin-A, AMPE I was more active in MTT assay as it portrays an IC

A sensitive double antibodies sandwich ELISA for the diagnosis and therapeutic evaluation of cervical cancer

Vascular endothelial growth factor (VEGF) is a highly specific factor for tumors growth. However, the study on the mechanism of VEGF in cervical cancer, and the correlation between the expression level of VEGF and the therapeutic evaluation, prognosis of cervical cancer is not clear till now. In this study, RT-qPCR and IHC were used to evaluate the abnormal expression of VEGF in cervical cancer. The survival plots of the VEGF expression related to OS were observed by using the KM plotter. The mAbs against VEGF were screened and identified by ELISA addicted test, indirect ELISA, Western-blot, and dot-ELISA. We designed and prepared the overlapping truncations (V1, V2, V3) of VEGF to identify the B cell epitopes. Then, the epitopes recognized by anti-VEGF mAbs were mapped and displayed on a 3D structure of VEGF by using the PyMOL software. The highly specific and sensitive sandwich ELISA was established to detect the total VEGF quantification in 206 clinical sera samples, thus to evaluate the changes of VEGF before and after chemoradiotherapy in cervical cancer patients. The VEGF was high expressed in cervical cancer tissues and cells, resulting a poor prognosis of cervical cancer. The mAbs 2E5 and 6D9 were selected with the titer of 1:256000 and 1:128000 respectively. The mAbs both had strong ability to combine with VEGF protein within 15 min and were identified as subclass IgG1 with κ-type light chains. 2E5 bound to V1 and V2, recognizing the N-terminal (1-121 aa) of VEGF, however 6D9 bound to V3, recognizing the C-terminal (116-174 aa) of VEGF. The 206 clinical samples were tested with the established VEGF-DAS-ELISA and calculated according to the equation (y = 0.0042088× + 0.105109, R A sensitive DAS-ELISA was established successfully, using which we can track the VEGF to evaluate the efficacy and estimate prognosis of cervical cancer. It is helpful for the diagnosis, therapeutic evaluation and prognosis of cervical cancer.

TLR8 and TLR9 gene polymorphisms and the risk of high-grade serous ovarian cancer

High-grade serous ovarian carcinoma (HGSOC) is the most prevalent and lethal histotype of epithelial ovarian cancer (EOC). Single nucleotide polymorphisms (SNPs) in Toll-like receptor (TLR) genes may serve as important markers of susceptibility to numerous cancers. We explored the frequency of TLR8 and TLR9 polymorphisms in 325 women and determined their role in susceptibility to EOC and viral infection. The group of patients with EOC included 93 HGSOC and 32 non-HGSOC cases. TLR8 rs3764879, TLR8 rs3764880, TLR9 rs352139, and rs352140 SNPs were genotyped using the allelic discrimination method. The homozygous recessive genotypes for TLR8 rs3764879 and TLR9 rs352139 SNPs were more common in patients with EOC, compared to healthy women, and increased the risk of ovarian cancer (p = 0.0001 and p G) was associated with a five-fold increased risk of HGSOC (p = 0.0001). A mutation in at least one allele of the TLR8 rs3764879 was also associated with a higher level of TLR8 expression in tumor tissues (p = 0.0008). The present study demonstrated a strong association between the TLR8 -129C>G SNP and an increased risk of the HGSOC subtype.

Rosa rugosa polysaccharide induces autophagy-mediated apoptosis in human cervical cancer cells via the PI3K/AKT/mTOR pathway

The aim of this study was to investigate the effect of a polysaccharide from Rosa rugosa Thunb. on human cervical cancer cells (HCCCs) and the underlying mechanism. Here, a novel Rosa rugosa polysaccharide, named as RRP, was purified from Rosa rugosa petals. RRP consisted of glucose, galacturonic acid, mannose, rhamnose, galactose, arabinose, xylose, and glucuronic acid (molar ratio: 7.78:7.59:4.23:3.22:3.15:1.65:1.00), with Mw of 327.92 kDa. RRP remarkably inhibited cell proliferation, migration, and cell cycle arrest in HeLa and SiHa cells. Furthermore, RRP induced apoptosis by activating the caspase family of proteins and mediating the reactive oxygen species (ROS)-mediated mitochondrial pathway. In addition, RRP was found to dose-dependently induce autophagy, which occurred prior to apoptosis. RRP also primarily induced autophagy-mediated apoptosis in HCCCs via the PI3K/AKT/mTOR pathway. Thus, RRP might serve as a legitimate therapeutic drug candidates against human cervical cancer.

Structural and anti-ovarian cancer insights into the immunoglobulin G-glabridin nanocomplex

In this study, the formation of the immunoglobulin G-glabridin (IgG-GB) complex and nanocomplex was analyzed by assessing the structure, stability, solubility, and anticancer effects against the human epithelial ovarian cancer cell line, SKOV3. The hydrodynamic sizes of the prepared IgG-GB nanocomplex were 190.1 ± 25.68 nm (PDI: 0.19 ± 0.02), and the solubility levels of GB in the free and nanoformulated forms were 97.28 μg/mL and 368.95 ± 59.63 μg/mL, respectively. Additionally, the IgG-GB nanocomplex exhibited a slower and more sustained release of GB in a pH-sensitive manner. Spectroscopic measurements indicated logK

Applications of starch-based mucoadhesive drug delivery systems in cancer management

A novel targeted anticancer drug delivery strategy: Cnidium officinale polysaccharide conjugated with carboxymethyl-5-fluorouracil and folic acid for ovarian cancer therapy

To mitigate adverse reactions induced by 5-fluorouracil (5-FU), Cnidium officinale fraction 2 (F2) polysaccharides served as the macromolecular carrier, facilitating its reaction with carboxymethyl-5-fluorouracil (C-5-FU) for producing F2-C-5-FU. Subsequently, this compound could react with folic acid (FA) through the ester bond, forming F2-C-5-FU-FA, as verified through NMR analysis. The in vitro anticancer efficacy of F2-C-5-FU-FA was evaluated using SKOV-3 cells that expressed folate receptor (FR) and FR-deficient A549 cells, showing greater cytotoxicity in the SKOV-3 cell line due to the FRs on the cell membrane. In vivo experiments were conducted on SKOV-3-bearing xenograft mice using an in vivo imaging system (IVIS). Animals injected with F2-C-5-FU-FA exhibited significantly stronger targeting of tumor tissue compared to those injected with F2-C-5-FU. These findings highlighted enhanced drug delivery and accumulation in targeted tumor regions facilitated by folate-targeted conjugates. Moreover, F2-C-5FU-FA showed reduced cardiac toxicity in mice and minimal spleen accumulation, indicating a negligible effect on the immune system. Overall, this study introduced a novel strategy for achieving highly efficient anticancer drug delivery into tumor cells that express FR.

TRIM27 promotes ovarian cancer progression through destabilizing AMPK and thus inactivating the cGAS/STING signaling pathway

Ovarian cancer (OV) is a highly malignant gynecologic malignancy with a poor prognosis, primarily due to late-stage diagnosis and therapeutic resistance. Tripartite motif-containing 27 (TRIM27), a member of the TRIM protein family, acts as a bifunctional regulator in various cancers. However, its role in OV remains underexplored. This study demonstrated that TRIM27 is significantly upregulated in OV tissues and cell lines. Functional assays utilizing both gain- and loss-of-function approaches revealed that TRIM27 depletion inhibits ovarian cancer cell proliferation, migration, invasion, and epithelial-to-mesenchymal transition (EMT). Mechanistic investigations, including RNA sequencing, immunoprecipitation, mass spectrometry, and in vivo ubiquitination assays, identified TRIM27 as a ubiquitin ligase that mediates K48-linked ubiquitination and subsequent proteasomal degradation of AMPKα, thereby suppressing the cGAS-STING signaling pathway. These results established TRIM27 as a pivotal oncogenic driver in OV through immune surveillance evasion. Additionally, elevated TRIM27 expression was associated with poor clinical outcomes, suggesting its potential as both a novel prognostic biomarker and therapeutic target for ovarian cancer.

The dual-edged sword: AlkB homolog 5-mediated autophagy regulation in cancers - molecular mechanisms and therapeutic implications: A review

RETRACTED: Transferrin-guided liposomal nanocarriers: A strategy for targeted cancer treatment

ATAD2 bromodomain in cancer therapy: current status and future perspectives

Development of novel prognostic protein signatures in ovarian cancer: Molecular structure and immune function of AQP5 protein and CTDP1 protein

Ovarian cancer is a serious gynecological malignancy, and early identification of prognostic markers is critical to improve clinical outcomes. Aquaporin 5 (AQP5) and cell cycle regulatory protein CTDP1 are considered as potential prognostic protein markers, but their specific molecular structure and immune function have not been thoroughly studied. The aim of this study was to investigate the molecular structure of AQP5 and CTDP1 and their immune function in ovarian cancer, to evaluate their potential as prognostic markers, and to provide new ideas for the diagnosis and efficacy monitoring of ovarian cancer. Cox regression analysis and LASSO regression were used to construct the risk prognosis model, and the preliminary verification was carried out. Finally, cell culture and high-resolution gene expression analysis were used to investigate the expression of AQP5 and CTDP1 and their roles in the immune microenvironment. The results showed that AQP5 and CTDP1 were highly expressed in ovarian cancer cell lines and were closely related to tumor immune invasion. The immunomicroenvironment analysis based on GRN showed that they showed a positive correlation with tumor-related immune cells. Through the constructed risk model, AQP5 and CTDP1 significantly affect patient prognosis, suggesting their potential as prognostic markers.

Protein-based nanocarriers for paclitaxel (PTX) delivery in cancer treatment: A review

In silico screening and identifying phytoconstituents of Withania somnifera as potent inhibitors of BRCA1 mutants: A therapeutic against breast cancer

Alginate-based NPs for targeted ovarian cancer therapy: Navigating current progress and biomedical applications

Ovarian cancer continues to be one of the most lethal gynecological malignancies, with earlier symptoms that are frequently subtle, resulting in detection at late stages. Although there are several traditional treatments, patients do not respond well to them owing to serious side effects. Alginate, a polysaccharide extracted from brown seaweed (a natural polymer), has gained significant attention as an ideal biopolymer for developing drug delivery systems because of its nontoxicity, biodegradability, and ease of manipulation. Alginate-based NPs (ABNPs) represent a new strategy for the targeted treatment of ovarian cancer, increasing the efficacy of chemotherapeutic agents in tumor cells while reducing systemic toxicity. Current strategies to exploit ABNPs relate to their capability to encapsulate different types of payloads, including small-molecule drugs, proteins, and genetic materials. Functionalization with targeting peptides, antibodies, or FA imparts selective affinity for ovarian cancer cells, and hence, a targeted chemotherapeutic approach. Alginate NPs are a versatile and potent platform for the targeted treatment of ovarian cancer, integrating drug delivery into diagnostics, as well as gene therapy. This review presents the latest research trends and an understanding of the characteristic features and functions of ABNPs in targeted delivery against ovarian cancer.

Deciphering the transcriptional alterations in high grade serous ovarian cancer upon catalytic inactivation of protein kinase D

To study the transcription alterations in high grade serous ovarian cancer upon catalytic inactivation of protein kinase D (PKD). PKD was catalytically inactivated in HGSOC cells OVCAR8 and SKOV3 by two highly selective, small molecule inhibitors CRT0066101, kb-NB142-70 and RNASeq analysis was performed to identify genes being differentially expressed upon this treatment. Gene Ontology and pathway analysis of the significantly differentially expressed transcripts were performed to identify the enriched biological process, molecular functions, and pathways. Comparative analysis identified 264 differentially expressed genes (131 and 133 genes up and downregulated, respectively) common among two PKD-inactivated HGSOC cell lines. Gene ontology (GO) analysis showed significantly enriched and functionally relevant physiological/biological processes including cell division, regulation of cell cycle and protein transport and chromatin organization. Molecular functions enriched in both cell lines after PKD inactivation were protein binding, ATP binding, protein kinase binding, transcription corepressor activity, chromatin binding, mRNA binding, ubiquitin protein ligase binding, microtubule binding and transcription factor binding. Among many, pathway analysis identified genes regulating cell proliferation, cell cycle and extracellular matrix remodelling - three paramount cellular processes that are dysregulated in HGSOC cells treated with PKD inhibitors. Collectively, our results showed that PKD and its downstream targets positively drive several tumorigenesis-associated cellular/physiological functions and could be therapeutically targeted against a lethal pathology like HOSOC.

Condensed tannins from Salix babylonica L. leaves induce apoptosis of human ovarian cancer cells through mitochondrial and PI3K/AKT/ERK signaling pathways

Condensed tannins, natural antioxidants, are widely known for their antitumor activity with low toxicity. However, the antitumor mechanism of Salix babylonica leaf condensed tannins (SCTs) remains unclear. Here, we purified bioactive SCTs and analyzed their structural characteristics, antitumor effects on human ovarian cancer (OC) cells as well as related potential mechanism. FT-IR, ESI-MS, and HPLC analyses demonstrated that SCTs primarily consist of procyanidins with (epi)catechin as the main flavan-3-ol extension unit. SCTs significantly inhibited the proliferation and migration of OVCAR3 and A2780 cells, induced G0/G1 cell cycle arrest, and promoted apoptosis. SCTs induced apoptosis through the mitochondrial apoptotic pathway by decreasing mitochondrial membrane potential, increasing intracellular reactive oxygen species generation, elevating the Bax/Bcl-2 ratio, and activating caspase-3. Network pharmacology analysis speculated that SCTs exert anti-ovarian cancer effects by targeting multiple targets and pathways, among which the PI3K/AKT/ERK pathway may be the main pathway of action. Western blot confirmed that SCTs inhibited the phosphorylation of AKT, MEK, and ERK. Moreover, SCTs dose-dependently impaired OVCAR3 tumor spheroid growth in three-dimensional culture models. These results suggested that SCTs induced apoptosis in OC cells by activating the mitochondrial-associated apoptosis pathway and inhibiting the PI3K/AKT/ERK signaling pathway, showing potential as therapeutic agents for OC.

A mini-overview of antibody-drug conjugates in platinum-resistant ovarian cancer: A preclinical and clinical perspective

Ovarian cancer is one of the most lethal gynaecologic cancers in China. Although platinum-based chemotherapy, PARP inhibitors and bevacizumab have prolonged long term survival and increased the overall response rate for platinum-sensitive ovarian cancer (PSOC), the treatment options for platinum-resistant ovarian cancer (PROC) are still limited. Antibody-drug conjugates (ADCs) represent a novel form of precision medicine, covalently linking specific monoclonal antibodies with potent cytotoxic payloads. Since mirvetuximab soravtansine (MIRV) received approval by the US Food and Drug Administration (FDA) as the first ADC for PROC in 2022, the development of novel ADCs for various targets in PROC has accelerated. In this review, we summarise the recent evidence and future prospects of ADCs targeting Folate Receptor alpha (FRα), mesothelin, cadherin-6, NaPi2b, human epidermal growth factor receptor 2 (HER2), dipeptidase 3 (DPEP3), B7-H4 (VTCN1), claudin-6 (CLDN6) and trophoblast antigen protein 2 (TROP2), in order to enhance our understanding of the clinical applications of ADCs and offer new insights for clinical practice and further research.

IL-15/IL-15Rα-secreting bioengineered adipocytes reactivate NK/CD8+ T cells in ovarian and colon cancer ascites

Malignant ascites (MA) presents a complex clinical challenge, linked inextricably to poor prognosis, chemoresistance, and metastasis of peritoneal carcinomatosis (PC). However, standard therapeutic approaches for managing or preventing MA secondary to PC remain unavailable. Here we display that a bioengineered adipocyte, encapsulating long-chain fatty acids and concurrently secreting IL-15 and IL-15 receptor α (IL-15Rα), markedly extends the half-life and bioactivity of IL-15. The bioengineered adipocyte consists of an IL-15-P2A-IL-15Rα-T2A-mCherry cDNA sequence stable transfected 3T3-F442A preadipocyte cell line and dcosahexaenoic acid (DHA) are simultaneously encapsulated in the lipid droplets of mature adipocytes, which release it into the MA upon tumor cell-triggered lipolysis. We demonstrate that the bioengineered adipocytes led to specific expansion and activation of NK/CD8

Chitosan/alginate polyelectrolyte complex hydrogels by additive manufacturing for in vitro 3D ovarian cancer modeling

Polyelectrolyte complexes (PECs) are self-assembled systems formed from oppositely charged polymers, used to create hydrogels for cell culture. This work was aimed at additive manufacturing 3D hydrogels made of a PEC between chitosan (Cs) and alginate, as well as their investigation for in vitro 3D ovarian cancer modeling. PEC hydrogels stability in cell culture medium demonstrated their suitability for long-term cell culture applications. Higher in vitro viability of two human ovarian cancer cell lines was detected at different time points on PEC hydrogels than on Cs hydrogels, used as a control. In addition, during the 63-day culture experiment, cells effectively colonized the scaffolds while retaining their aggressive tumor characteristics. A significantly lower sensitivity to cisplatin and eugenol, also when combined, was observed in the developed 3D ovarian cancer models, in comparison to what was achieved in relevant 2D cell cultures. The obtained results demonstrated therefore the suitability of the developed scaffolds for in vitro investigation of tumor modeling.

Integrating network pharmacology to investigate the mechanism of quercetin's action through AKT inhibition in co-expressed genes associated with polycystic ovary syndrome and endometrial cancer

Endometrial cancer (EC) is a common gynecological malignancy for which polycystic ovarian syndrome (PCOS) has been identified as a significant risk factor. Quercetin, a widely distributed natural flavonoid, has demonstrated potential therapeutic effects in managing both PCOS and EC. However, the specific molecular targets of quercetin in the context of PCOS comorbid with EC (PCOS-EC) remain poorly defined. This study aims to elucidate the therapeutic potential of quercetin for treating PCOS-EC using network pharmacology, molecular dynamics simulations, and in vitro assays. The intersection of 379 PCOS-EC-associated targets with 361 quercetin targets identified 47 potential therapeutic targets of quercetin for PCOS-EC. Gene Ontology enrichment analysis revealed the biological functions, while Kyoto Encyclopedia of Genes and Genomes identified the pathways potentially involved in quercetin's effects against PCOS-EC. Protein-protein interaction network analysis highlighted six overlapping targets, namely, ACTB, AKT1, EGFR, ESR1, PTGS2, and TP53. Molecular docking and molecular dynamics simulations indicated that quercetin bound with high affinity to the hub genes, with AKT1 emerging as a central target. In vitro experiments confirmed that quercetin treatment significantly downregulated AKT expression in EC cells. These findings elucidate potential targets and molecular mechanisms through which quercetin exerts its therapeutic effects.

Tanshinone I reprograms glycolysis metabolism to regulate histone H3 lysine 18 lactylation (H3K18la) and inhibits cancer cell growth in ovarian cancer

Salvia miltiorrhiza, the anticancer properties of these components are multifaceted, encompassing the inhibition of tumor growth, prevention of the metastatic spread of cancer cells, enhancement of the sensitivity of cancer cells to chemotherapy and radiation therapy, and the suppression of angiogenesis, which is crucial for tumor growth and survival. In the context of our recent study, we have discovered that tanshinone I, one of the active components of Salvia miltiorrhiza, possesses the ability to inhibit the proliferation of ovarian cancer cells, both in laboratory settings and within living organisms. To further understand the molecular mechanisms behind this effect, we conducted a comprehensive transcriptomic analysis. Our findings indicated that tanshinone I exerts its inhibitory action by downregulating the expression of genes associated with glycolysis. Specifically, tanshinone I decreased the expression of glycolysis-related genes such as HK2 (hexokinase 2), PFK (phosphofructokinase), ENO2 (enolase 2), and LDHA (lactate dehydrogenase A). Inhibiting lactate production by tanshinone I application reduced the level of histone H3 lysine 18 lactylation (H3K18la), which reduced the expression of tumor-associated genes, such as TTK, PDGFRβ, YTHDF2 and RUBCNL. In addition, tanshinone I alleviated the immunosuppressive tumor microenvironment. In summary, tanshinone I blocks glycolysis to regulate histone H3 lysine 18 lactylation (H3K18la), which inhibits ovarian cancer cell growth, revealing the anticancer mechanism of tanshinone I.

Core-shell structured magnetite carboxymethyl cellulose for cervical cancer treatment by maintaining methotrexate serum concentration

In this work, we attempted to improve the properties of magnetite carboxymethyl cellulose nanoparticles (Mag CMC NPs) through Ugi multicomponent reaction (MCR) to obtain magnetite carboxymethyl cellulose@functionalized carboxamide nanoparticles (Mag CMC@FCA NPs) as a new nano bio-carrier. Typically, at first Mag CMC NPs prepared by the co-precipitation method. Then by performing the Ugi MCR on Mag CMC NPs, the Mag CMC@FCA NPs achieved better properties in swelling ratio, loading efficiency and loading capacity. The prepared Mag CMC@FCA NPs characterized in detail. Evaluation of the prepared system functionality showed the swelling rate increased from 294 % to 1472 %. Furthermore, for methotrexate (MTX), loading efficiency increased from 24.62 % for Mag CMC NPs to 57.25 % for Mag CMC@FCA NPs, and the drug loading capacity increased from 1.23 % to 2.86 %. The loading of Ampicillin (AMP) and MTX has been observed to have a beneficial effect. When AMP is placed in the metabolic pathway of MTX, it prevents biodegradation of MTX up to 35 %, which results in a longer duration of high MTX concentration in the blood. Consequently, the toxicity of the prepared medication on healthy cells of the body is reduced, and the death rate is decreased to some extent.

Zein-PEG nanoparticles modified with hyaluronic acid for paclitaxel delivery in SKOV3 ovarian cancer cells

Ovarian cancer is a leading gynecological cancer globally. This study aimed to develop hyaluronic acid-modified polyethylene glycol conjugated zein nanoparticles (zein-PEG/HA NPs) to enhance paclitaxel (PTX) cytotoxicity in SKOV3 ovarian cancer cells. Zein-PEG, with its amphiphilic nature, self-assembled into micelles to encapsulate the hydrophobic PTX, while the PEG shell retained micelle stability and hemolytic resistance. PTX@zein-PEG micelles (17.2 ± 0.3 mV) were complexed with negatively charged HA through electrostatic interactions, resulting in PTX@zein-PEG/HA NPs with a negative zeta potential of -15.3 ± 1.1 mV. Cellular uptake of fluorescent zein-PEG/HA NPs was higher than zein-PEG micelles in CD44-overexpressing SKOV3 cells. Additionally, PTX@zein-PEG/HA NPs demonstrated significantly greater cytotoxicity than free PTX and PTX@zein-PEG micelles, with IC

Identification of prevention marker associated with DNA replication in ovarian cancer: Expression of MCM2 protein and bioinformatics analysis

Ovarian cancer is one of the types of gynecological cancers that is considered to be particularly dangerous. Ovarian cancer treatment has come a long way in recent years, but the disease is still quite likely to spread to other parts of the body. In this line of research, our goal is to pinpoint the shifts in gene expression profiles that are responsible for the avoidance of ovarian cancer. The dataset GSE54388 which was deposited in the Gene Expression Omnibus (GEO) database was processed in order to find differentially expressed genes (DEGs) that were present between human ovarian surface epithelium samples and tumor epithelial component samples. The weighted gene correlation network analysis, also known as WGCNA, was performed on the modules that were associated with the ovarian cancer group. The Gene Ontology (GO), the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis, and the Gene Set Enrichment Analysis (GSEA) were used to compile a summary of the DEGs that were found in the Venn analysis of the Royalbule module. This analysis found 186 genes that overlapped in the royal blue module. Using the cytohubba plug-in that is included in the Cytoscape software, the Protein-protein Interaction (PPI) network was created and then searched to identify hub genes. Based on these findings, it seems that 10 genes have a role as hub genes in the prevention of ovarian cancer.

Coaxial nanofibrous aerogel featuring porous network-structured channels for ovarian cancer treatment by sustained release of chitosan oligosaccharide

Ovarian cancer, the deadliest gynecological malignancy, primarily treated with chemotherapy. However, systemic chemotherapy often leads to severe toxic side effects and chemoresistance. Drug-loaded aerogels have emerged as a promising method for drug delivery, as they can improve drug solubility and bioavailability, control drug release, and reduce drug distribution in non-targeted tissues, thereby minimizing side effects. In this research, chitosan oligosaccharide (COS)-loaded nanofibers composite chitosan (CS) aerogels (COS-NFs/CS) with a porous network structure were created using nanofiber recombination and freeze-drying techniques. The core layer of the aerogel has a COS loading rate of 60 %, enabling the COS-NFs/CS aerogel to significantly inhibit the migration and proliferation of ovarian cancer cells (resulting in a decrease in the survival rate of ovarian cancer cells to 33.70 % after 48 h). The coaxial fiber's unique shell-core structure and the aerogel's porous network structure enable the COS-NFs/CS aerogels to release COS steadily and slowly over 30 days, effectively reducing the initial burst release of COS. Additionally, the COS-NFs/CS aerogels exhibit good biocompatibility, degradability (only retaining 18.52 % of their weight after 6 weeks of implantation), and promote angiogenesis, thus promoting wound healing post-oophorectomy. In conclusion, COS-NFs/CS aerogels show great potential for application in the treatment of ovarian cancer.

Injectable bio-multifunctional hyaluronic acid-based hydrogels loaded with poly ADP-ribose polymerase inhibitors for ovarian cancer therapy

The recent use of PARP inhibitors (PARPi) in the maintenance treatment of ovarian tumor has significantly improved the survival rates of cancer patients. However, the current oral administration of PARP inhibitors fails to realize optimal therapeutic effects due to the low bioavailability in cancerous tissues, and often leads to a range of systemic adverse effects including hematologic toxicities, digestive system reactions, and neurotoxicities. Therefore, the demand for an advanced drug delivery system that can ensure effective drug administration while minimizing these unfavorable reactions is pressing. Injectable hydrogel emerges as a promising solution for local administration with the capability of sustainable drug release. In this study, we developed an injectable hydrogel made from aminated hyaluronic acid and aldehyde-functionalized pluronic127 via Schiff base reaction. This hydrogel exhibits excellent injectability with short gelation time and remarkable self-healing ability, and is applied to load niraparib. The drug-loaded hydrogel (HP@Nir hydrogel) releases drugs sustainably as tested in vitro as well as displays significant anti-proliferation and anti-migratory properties on human epithelial ovarian cancer cell line. Notably, HP@Nir hydrogel effectively suppresses the growth of ovarian cancer, without significant adverse reactions as demonstrated in animal studies. Additionally, the developed hydrogel is gradually degraded in vivo for around 20 d, while maintaining good biocompatibility. Overall, the injectable hydrogel loaded with niraparib provides a secure and efficient strategy for the treatment and management of ovarian cancer.

Glutamine modified lipid nanoparticles loaded with GPX4 siRNA for cervical cancer targeting

Despite significant efforts to develop nanocarriers for siRNA delivery, clinical application in cancer therapy has been hindered by inadequate tumor-targeting specificity, with cervical cancer particularly affected by poor tumor-specific targeting. Our previous work identified aberrant glutamine metabolism and ASCT2 overexpression in cervical cancer, providing a rationale for designing glutamine-ASCT2 interaction-based delivery systems. Based on this, we developed a self-fabricated microfluidic device for the preparation of lipid nanoparticles (LNP) and constructed a glutamine-modified lipid nanoparticle (GLN-LNP) for targeted siRNA delivery to cervical cancer. GLN-LNP exhibited significantly enhanced cellular uptake in both 2D cell monolayers and 3D tumor spheroid models. The competitive inhibition of uptake by free glutamine and the significant inhibition by an ASCT2-specific inhibitor V-9302 further confirm the critical role of the glutamine-ASCT2 interaction in facilitating LNP transport. GLN-LNP significantly decreased GPX4 expression in vitro at both transcriptional and translational level. In vivo results illustrated GLN-LNP had enhanced tumor accumulation capability compared to PEG-LNP, which has no glutamine modification. Additionally, GLN-LPN induced obvious in vivo GPX4 knockdown. These findings demonstrate GLN-LNP as a promising preclinical delivery system for cervical cancer, highlighting their potential to advance the clinical development of siRNA-based therapeutic.

Integrin β8: A novel prognostic biomarker for ovarian cancer identified through multi-omics-based prognostic models and experimental validation

This study aimed to identify specific prognostic biomarkers for ovarian cancer (OC), develop a prognostic model, and validate a key candidate target. We established a co-expression network using single-cell transcriptomic data and high-dimensional weighted gene co-expression network analysis (hdWGCNA). A 13-gene prognostic signature was constructed via Cox/LASSO regression, effectively stratifying patients into high- and low-risk groups with distinct prognoses (external validation 1-year AUC = 0.83). Comprehensive analyses including CIBERSORT, pRRophetic, GSVA/GSEA, and TIDE assessment revealed that high-risk patients exhibited poorer outcomes, reduced CD8+ T cell infiltration, diminished sensitivity to multiple targeted agents, activation of Hedgehog, NF-κB, and PI3K-Akt pathways, and lower predicted immunotherapy response. A nomogram incorporating the risk score demonstrated good prognostic utility. The risk score constituted an independent prognostic factor (multivariate HR = 1.98). From the signature, ITGB8 was selected for experimental validation. ITGB8 demonstrated significant overexpression in OC tissues and cell lines. Its knockdown suppressed OC cell proliferation, invasion, and migration in vitro, and tumorigenicity in vivo. Furthermore, we identified that ITGB8 promotes invasion by activating the PI3K-AKT-NF-κB signaling pathway, as evidenced by reduced phosphorylation upon knockdown and rescued invasion with a PI3K agonist. This work successfully establishes a validated OC prognostic model and identifies ITGB8 as a novel prognostic biomarker and functional oncogene, supporting its future investigation as a candidate therapeutic target.

Application progress of tRNA modification in gynecological tumors: A review

The conventional role of tRNA as a pivotal molecule in protein synthesis is well-established. However, recent studies have unveiled a previously underappreciated function of tRNA chemical modifications in tumor biology, particularly in tumor initiation, progression, and metastasis. Gynecological malignancies represent a significant threat to women's health. Despite advances in medical technology, gynecological malignancies remain difficult to manage, partly due to limited treatment options. Delayed diagnosis and high tumor heterogeneity further contribute to poor prognosis. This review focuses on tRNA modifications in gynecological cancers, including ovarian, cervical, and endometrial cancers. It systematically elucidates the expression profiles and regulatory mechanisms of various tRNA modifications. Additionally, it explores their correlation with malignant characteristics-such as enhanced tumor cell proliferation, drug resistance, invasion, and metastasis. Furthermore, it explores the translational potential of these modifications as biomarkers, therapeutic targets, and prognostic indicators, and the potential links in the TME, metabolic reprogramming, and Immunotherapeutic Response, offering a novel perspective for the precise diagnosis and management of gynecological tumors.

Emodin exerts antitumor effects in cervical cancer cells by reprogramming phospholipid metabolism through modulation of H3K27ac and H3K27me3

Emodin, a natural compound derived mainly from Reynoutria japonica (Huzhang), has demonstrated notable antitumor effects, though its epigenetic regulatory mechanisms in cervical cancer remain largely unclear. In this study, we show that emodin suppresses cervical cancer cell proliferation and induces oxidative stress. Integrated transcriptomic and metabolomic analyses further demonstrated that emodin markedly disrupted lipid metabolism, particularly by increasing phospholipid accumulation and promoting phospholipid peroxidation. Epigenetic profiling using Western blotting showed that emodin treatment altered global histone modification patterns, with notable increases in H3K27ac and H3K27me3 levels. Subsequent CUT&Tag analysis combined with ChIP-qPCR validation indicated that emodin modulates these two histone marks to regulate the transcription of key phospholipid metabolism-related genes, thereby contributing to enhanced phospholipid peroxidation and antitumor activity. Together, these findings provide new insights into the epigenetic antitumor mechanisms of emodin and highlight potential histone modification targets involved in phospholipid metabolism.

Galectin-3 suppresses CD8+ T cells function via myeloid-derived suppressor cells recruitment in cervical cancer

The tumor immune microenvironment is crucial in tumor development. Galectin-3 (GAL3), a beta-galactoside-binding lectin and tumor secretory protein, is increasingly recognized as a key mediator of immunosuppression in various cancers; however, its role in cervical cancer (CC) immune escape has not been well studied. This study investigates GAL3 regulation of myeloid-derived suppressor cells (MDSCs) through immune infiltration, flow cytometry, cytokine screening, and animal models. Particularly, GAL3 was upregulated in CC samples and was significantly correlated with lymph node metastasis, recurrence, and survival. Correlation analysis showed that GAL3 expression was correlated with the aggregation of MDSCs. Patients with high MDSCs infiltration have a poor prognosis. Mechanistically, GAL3 promoted MDSCs recruitment by activating STAT3/Akt signaling pathway. Additionally, MDSCs inhibited CD8

Heme oxygenase-1 (HO-1) depletion promotes ferroptosis to reverse cisplatin-resistance via enhancing NCOA4-mediated ferritinophagy in ovarian cancer

Ovarian cancer remains the deadliest gynecological malignancy, with cisplatin resistance being a major therapeutic challenge. This study investigates the role of heme oxygenase-1 (HO-1) in cisplatin resistance and its regulation mechanisms through ferroptosis and ferritinophagy. In this study, significant overexpression of HO-1 was observed in cisplatin-resistant ovarian cancer cells and tissues, correlating with poor patient prognosis. Using HO-1 inhibitors and siRNA-mediated knockdown, it was demonstrated that HO-1 depletion reversed cisplatin resistance by promoting ferroptosis, a form of iron-dependent cell death. Mechanistically, HO-1 knockdown increased nuclear receptor coactivator 4 (NCOA4)-mediated ferritinophagy, resulting in elevated labile iron pool (LIP) levels, lipid peroxidation, and reduced glutathione (GSH) levels. Xenograft models further confirmed that HO-1 inhibition synergizes with cisplatin to suppress tumor growth by enhancing ferritinophagy-mediated ferroptosis. These findings highlight HO-1 as a key regulator of iron metabolism and ferroptosis in cisplatin-resistant ovarian cancer. In conclusion, our study demonstrates that HO-1 depletion enhances ferroptosis, reversing cisplatin resistance in ovarian cancer through NCOA4-mediated ferritinophagy. The combination of cisplatin with HO-1 inhibition emerges as a promising strategy to overcome cisplatin resistance, offering a potential therapeutic avenue for ovarian cancer treatment.

A review on the role of epidermal growth factor signaling in the development, progression and treatment of cervical cancer

The sub-committee constituted by the Indian Council of Medical Research (ICMR) for the management of cervical cancer (CC) detailed in the consensus document (2016) reported CC as a significant cause of morbidity and mortality in women. The incidence of an increase in CC and associated mortality in women is a major cause of cancer. To date, human papilloma viral (HPV) infection accounts for more than 99% of CC. However, there are individuals infected with HPV do not develop CC. There is a greater correlation between HPV infection and upregulation of the epidermal growth factor receptor (EGFR) signaling cascade during the initiation, sustenance, and progression of CC. Therefore, EGFR is often targeted to treat CC using tyrosine kinase inhibitors (TKIs) and monoclonal antibodies (mAB). The current review analyzed the existing clinical/pre-clinical studies and the significance of EGFR abundance using the Kaplan-Meier (KM) survival plot analysis for disease-free survival (DFS) and overall survival (OS). We performed a series of bioinformatics analyses to screen the crucial role of the EGFR gene in CC. Further, different transcription factors that are dysregulated due to EGFR abundance and their relevance were determined using computational tools in this review. Endogenous microRNAs (miRNA) that undergo changes due to alterations in EGFR during CC were identified using computational database and consolidated the information obtained with the published in the area of miRNA and EGFR with special reference to the initiation, sustenance and progression of CC. The current review aims to consolidate contemporary approaches for targeting CC using EGFR and highlight the current role of miRNA and genes that are differently regulated during CC involving EGFR mutations. Potential resistance to the available EGFR therapies such as TKIs and mABs and the need for better therapies are also extensively reviewed for the development of newer therapeutic molecules with better efficacy.

EGFR-targeted humanized single chain antibody fragment functionalized silica nanoparticles for precision therapy of cancer

Causal relationship between 91 circulating inflammatory proteins and gynecological diseases: A two-sample bidirectional Mendelian randomization study

Immunomodulatory and anti-ovarian cancer effects of novel astragalus polysaccharide micelles loaded with podophyllotoxin

Ovarian cancer, a highly lethal form of gynecological cancer globally, has witnessed notable advancements in its treatment through the integration of nanotechnology and immunotherapy. Here, we designed a novel astragalus polysaccharide vector (PDA), encapsulating podophyllotoxin (PPT), and modifying methotrexate (DSPE-PEG

Circular RNAs as emerging players in cervical cancer tumorigenesis; A review to roles and biomarker potentials

Cervical cancer is the most lethal gynecological cancer among women worldwide. Most of the patients are diagnosed at the advanced stages due to late diagnosis and lack of accessible and valuable approaches for early detection of the disease. Circular RNAs (circRNAs) are a distinguishable class of non-coding RNAs with characteristic loop structures. Although their function has not been completely elucidated; however, recent evidence has suggested regulatory functions for circRNAs on gene expression controlling various biological functions like cell growth and apoptosis, development, embryogenesis, and pathogenesis of human diseases particularly cancers. Studies show the role of dysregulated circRNAs in biological processes including cell proliferation, migration, invasion, apoptosis, angiogenesis, and chemoresistance contributing to affect tumorigenesis in ovarian cancer cells, animal, and clinical studies. These effects can be defined as consistent with several tumorigenesis characteristics, which are defined as "hallmarks of cancer". Additionally, dysregulated circRNAs exhibit prognostic, and diagnostic potentials both in the prediction of prognosis in ovarian cancer patients, and also their discrimination from healthy individuals. Furthermore, targeting circRNAs has shown positive results in the suppression of malignant features of cancer cells, and also in overcoming chemoresistance. In this review, I have gathered the majority of studies evaluating the role of circRNAs in the development, and progression of cervical cancer, and also have discussed prognostic, diagnostic, and therapeutic potentials of circRNAs for clinical applications in cervical cancer patients.

Targeting and neutralizing human epididymis protein 4 by novel nanobodies to suppress ovarian cancer cells and attenuate cisplatin resistance

Human epididymis protein 4 (HE4) is a glycoprotein secreted by epithelial ovarian cancer (EOC) cells and is a novel and specific biomarker for diagnosing and prognosing EOC. Previous studies have shown that overexpression of HE4 is correlated with EOC tumorigenesis and chemoresistance. However, less has been reported regarding the direct effect of the secreted HE4 protein as an autocrine factor in EOC cells. Here, we investigated the molecular mechanism of the secretory form of HE4 on the growth of EOC cells by applying nanobodies with a targeted interaction of free HE4. Three anti-HE4 nanobodies were selected from an immune library by phage display. HE4 secreted by serum-free cultured OVCAR3 cells increased and was effectively neutralized by anti-HE4 nanobodies, which inhibited cell viability. Treatment with the anti-HE4 nanobody 1G8 decreased Bcl-2 expression and increased BAX, cleaved PARP, and p53 levels, resulting in apoptosis of OVCAR3 cells. Moreover, 1G8 significantly improved the cisplatin response of OVCAR3 cells. Our data suggest that secretory HE4 played a novel pro-survival autocrine role and was a target of the anti-HE4 nanobody to improve the therapeutic effects of cisplatin-based chemotherapy.

Arabinogalactan derived from Lycium barbarum fruit inhibits cancer cell growth via cell cycle arrest and apoptosis

Previous studies have shown that crude polysaccharides from the Lycium barbarum fruit could inhibit cancer cell growth, but the major effective constituents are yet to be identified. In this study, we compared the effects of L. barbarum fruit polysaccharide fractions on the growth of hepatoma cells (SMMC-7721 and HepG2), cervical cancer cells (HeLa), gastric carcinoma cells (SGC-7901), and human breast cancer cells (MCF-7). LBGP-I-3 showed stronger inhibitory effects on MCF-7 cells (cell viability of 48.96%) than SMMC-7721 (cell viability of 78.91%) and HeLa cells (cell viability of 55.94%), and had no effect on HepG2 and SGC-7901 cells. In addition, LBGP-I-3 had no inhibitory effect on normal liver cells (L02, cell viability of 115.58%). Investigation of the underlying mechanism suggested that LBGP-I-3 inhibited the growth of cancer cells by cell cycle arrest and apoptosis. LBGP-I-3 arrested the cell cycle at the G0/G1 phase, altered mitochondrial function, activated oxidative stress, and regulated the MAPK signaling pathway to induce apoptosis. Thus, LBGP-I-3 may be a potential functional food ingredient for the prevention of cancer without toxicity to normal cells in vitro. These results could help further elucidate the structure-activity relationship of L. barbarum fruit polysaccharides and functional food development.

Purification, characterization and anticancer activities of exopolysaccharide produced by Rhodococcus erythropolis HX-2

In the present study, an exopolysaccharide (EPS) producer Rhodococcus erythropolis HX-2 was isolated from Xinjiang oil field, China. The HX-2 EPS (name HPS) production reached 8.957 g/L by RSM in MSM medium. The HPS was purified by ethanol precipitation and fractionation by DEAE-Cellulose and Sepharose column, the yield of HPS was 3.736 g/L. HPS composed by glucose, galactose, fucose, mannose and glucuronic acid. FT-IR spectroscopy indicated the presence of a large amount of hydroxyl groups. NMR spectroscopy indicated the existence of both α and β-configuration for sugar moieties present in HPS. The degradation temperature (255.4 °C) of the HPS was determined by thermogravimetric analysis (TGA). A reticular structure of HPS was observed by SEM and the AFM analysis of the HPS revealed straight chains line. Meanwhile, the WSI and WHC of HPS were 92.15 ± 3.05% and 189.45 ± 5.65%, respectively. Finally, In vitro anticancer activity purified EPS was evaluated on L929 normal cells, A549 cancer cells, SMMC-7721 liver cancer cells and Hela cervical cancer cell. HPS inhibited the growth of cancer cells in a certain concentration without damage to normal cells. These characteristics indicate that its potential application value in food, industry and pharmaceutical application.

Exosomal LINC00958 maintains ovarian cancer cell stemness and induces M2 macrophage polarization via Hedgehog signaling pathway and GLI1 protein

Long non-coding RNA (lncRNA) LINC00958 has been reported to promote many gynecological cancers, but its detailed function in OC remains unclear. Cancer stem cells (CSCs) and tumor-associated macrophages (TAMs) have been reported to participate in the occurrence and metastasis of cancers. We want to explore the effects of exosomal LINC00958 on cell stemness and macrophage polarization in OC. LINC00958 expression was first verified in OC cells and its function on cell stemness was verified by subcellular fractionation analysis, sphere formation assay and so on. Exosomal LINC00958 was secreted from OC cells and the model of M2 macrophage polarization was established to further verify the impact of exosomal LINC00958 on the cell stemness and macrophage polarization of OC cells using several mechanism experiments including flow cytometry, RNA pulldown, luciferase reporter assays and so on. LINC00958 was up-regulated in OC cells and exosomal LINC00958 enhanced the stem cell-like properties of OC cells and M2 macrophage polarization. Furthermore, LINC00958 combined with glioma-associated oncogene homolog 1 (GLI1) to activate Hedgehog pathway, thereby promoting M2 polarization. Exosomal LINC00958 maintained OC cell stemness and induced M2 polarization via the Hedgehog signaling pathway.

Preliminary exploration of the anti-ovarian cancer activity of peptides derived from bovine bone collagen hydrolysate and its related mechanisms

Ovarian cancer, a malignant tumor that poses a significant threat to women's health, has seen a rise in incidence, prompting the urgent need for more effective treatment. This study primarily aimed to explore the potential of bovine collagen peptides in inhibiting ovarian cancer. The investigation in this study began with the identification of 268 peptide sequences through LC-MS/MS, followed by a screening process using molecular docking techniques to identify potential peptides capable of binding to EGFR. Subsequently, a series of experiments were performed, demonstrating the inhibitory effects of the peptide GPAGADGDRGEAGPAGPAGPAGPR on the proliferation of ovarian cancer cells. Transcriptomic analysis further revealed that this peptide can regulate cholesterol metabolism in ovarian cancer cells. Finally, a combination of time-resolved fluorescence resonance energy transfer, isothermal titration calorimetry, molecular docking, and molecular dynamics simulations were utilized to validate the ability of this peptide to bind to the epidermal growth factor receptor (EGFR) and impede the binding of epidermal growth factor (EGF) and EGFR.

A review of Glycogen Synthase Kinase-3 (GSK3) inhibitors for cancers therapies

The transcription factor HAND1 suppresses endometrial cancer progression by regulating fatty acid β-oxidation via c-MET

Endometrial cancer (EC) is the second most common malignancy in the female reproductive system, yet its pathogenesis remains unclear. The transcription factor HAND1, a potential tumor suppressor, has an undefined role in EC progression. In this study, we found that HAND1 expression was significantly downregulated in EC tissues and negatively correlated with the malignant behaviors of EC cells. Transcriptomic and metabolomic analyses revealed that HAND1 overexpression markedly downregulated c-MET expression and facilitated the accumulation of acylcarnitine. Mechanistic studies demonstrated that c-MET could rescue the effects of HAND1 on EC cell proliferation, migration, invasion, and tumorigenicity. Further investigation revealed that upregulation of HAND1 significantly suppressed CPT2 expression via inhibition of c-MET, resulting in attenuated fatty acid β-oxidation (FAO) activity, reduced expression of electron transport chain complexes, diminished ATP synthesis, and a decline in mitochondrial membrane potential. Collectively, this study elucidates the molecular mechanism by which the HAND1/c-MET axis regulates EC progression through the modulation of FAO. This provides a novel perspective for understanding the pathogenesis of EC and offers potential biomarkers for developing novel diagnostic and therapeutic strategies for EC.

MTA1-DT promotes endometrial cancer growth by modulating G2/M-related gene transcription via PURα

In recent years, patients with early endometrial cancer (EC) can achieve a good prognosis through surgery. However, advanced and recurrent cases have still posed significant therapeutic challenges. This study aimed to investigate the biological function of long non-coding RNAs (lncRNAs) in EC and elucidate its underlying molecular mechanism. Through quantitative reverse transcription polymerase chain reaction (RT-qPCR) analysis, functional assays in cell lines, and bioinformatics approaches, we identified lncRNA MTA1-DT as a novel oncogenic factor in EC progression. RNA-seq and RT-qPCR analysis demonstrated that MTA1-DT was significantly upregulated with a 5-fold increase in EC cell lines compared to normal controls. Functional studies revealed that MTA1-DT promoted cell proliferation and migration. Mechanistically, we demonstrated that MTA1-DT physically interacted with purine-rich element binding protein-alpha (PURα) and facilitated its nuclear translocation, thereby enhancing its transcription factor activity. This nuclear accumulation of PURα promoted the transcription of downstream G2/M related genes, particularly EGF, leading to accelerated tumor growth. Thus, these results indicate that MTA1-DT exerts its oncogenic effects in EC through regulation of the cell cycle. Our findings establish MTA1-DT as a promising therapeutic target for EC treatment and provide new insights into the molecular mechanisms underlying EC progression.