Comprehensive Neurotoxicity of Lead Halide Perovskite Nanocrystals in Nematode Caenorhabditis elegans.

To date, all-inorganic lead halide perovskite quantum dots have emerged as promising materials for photonic, optoelectronic devices, and biological applications, especially in solar cells, raising numerous concerns about their biosafety. Most of the studies related to the toxicity of perovskite quantum dots (PeQDs) have focused on the potential risks of hybrid perovskites by using zebrafish or human cells. So far, the neurotoxic effects and fundamental mechanisms of PeQDs remain unknown. Herein, a comprehensive methodology is designed to investigate the neurotoxicity of PeQDs by using Caenorhabditis elegans as a model organism. The results show that the accumulation of PeQDs mainly focuses on the alimentary system and head region. Acute exposure to PeQDs results in a decrease in locomotor behaviors and pharyngeal pumping, whereas chronic exposure to PeQDs causes brood decline and shortens lifespan. In addition, some abnormal issues occur in the uterus during reproduction assays, such as vulva protrusion, impaired eggs left in the vulva, and egg hatching inside the mother. Excessive reactive oxygen species formation is also observed. The neurotoxicity of PeQDs is explained by gene expression. This study provides a complete insight into the neurotoxicity of PeQD and encourages the development of novel nontoxic PeQDs.

PPAR-γ agonists reactivate the ALDOC-NR2F1 axis to enhance sensitivity to temozolomide and suppress glioblastoma progression.

Glioblastoma (GBM) is a type of brain cancer categorized as a high-grade glioma. GBM is characterized by limited treatment options, low patient survival rates, and abnormal serotonin metabolism. Previous studies have investigated the tumor suppressor function of aldolase C (ALDOC), a glycolytic enzyme in GBM. However, it is unclear how ALDOC regulates production of serotonin and its associated receptors, HTRs. In this study, we analyzed ALDOC mRNA levels and methylation status using sequencing data and in silico datasets. Furthermore, we investigated pathways, phenotypes, and drug effects using cell and mouse models. Our results suggest that loss of ALDOC function in GBM promotes tumor cell invasion and migration. We observed that hypermethylation, which results in loss of ALDOC expression, is associated with serotonin hypersecretion and the inhibition of PPAR-γ signaling. Using several omics datasets, we present evidence that ALDOC regulates serotonin levels and safeguards PPAR-γ against serotonin metabolism mediated by 5-HT, which leads to a reduction in PPAR-γ expression. PPAR-γ activation inhibits serotonin release by HTR and diminishes GBM tumor growth in our cellular and animal models. Importantly, research has demonstrated that PPAR-γ agonists prolong animal survival rates and increase the efficacy of temozolomide in an orthotopic brain model of GBM. The relationship and function of the ALDOC-PPAR-γ axis could serve as a potential prognostic indicator. Furthermore, PPAR-γ agonists offer a new treatment alternative for glioblastoma multiforme (GBM).

The cytoplasmic expression of FSTL3 correlates with colorectal cancer progression, metastasis status and prognosis.

Follistatin-like (FSTL) family members are associated with cancer progression. However, differences between FSTL members with identical cancer types have not been systematically investigated. Among the most malignant tumours worldwide, colorectal cancer (CRC) has high metastatic potential and chemoresistance, which makes it challenging to treat. A systematic examination of the relationship between the expression of FSTL family members in CRC will provide valuable information for prognosis and therapeutic development. Based on large cohort survival analyses, we determined that FSTL3 was associated with a significantly worse prognosis in CRC at the RNA and protein levels. Immunohistochemistry staining of CRC specimens revealed that FSTL3 expression levels in the cytosol were significantly associated with a poor prognosis in terms of overall and disease-free survival. Molecular simulation analysis showed that FSTL3 participated in multiple cell motility signalling pathways via the TGF-ß1/TWIST1 axis to control CRC metastasis. The findings provide evidence of the significance of FSTL3 in the oncogenesis and metastasis of CRC. FSTL3 may be useful as a diagnostic or prognostic biomarker, and as a potential therapeutic target.

Gold Nanoparticles as a Biosensor for Cancer Biomarker Determination.

Molecular biology applications based on gold nanotechnology have revolutionary impacts, especially in diagnosing and treating molecular and cellular levels. The combination of plasmonic resonance, biochemistry, and optoelectronic engineering has increased the detection of molecules and the possibility of atoms. These advantages have brought medical research to the cellular level for application potential. Many research groups are working towards this. The superior analytical properties of gold nanoparticles can not only be used as an effective drug screening instrument for gene sequencing in new drug development but also as an essential tool for detecting physiological functions, such as blood glucose, antigen-antibody analysis, etc. The review introduces the principles of biomedical sensing systems, the principles of nanomaterial analysis applied to biomedicine at home and abroad, and the chemical surface modification of various gold nanoparticles.

The CHST11 gene is linked to lung cancer and pulmonary fibrosis.

BACKGROUND: The abnormal modification of chondroitin sulfate is one of the leading causes of disease, including cancer progression. During chondroitin sulfate biosynthesis, the CHST11 enzyme plays a vital role in its modification, but its role in cancer is not fully understood. Therefore, understanding the relationship between CHST11 and pulmonary-related diseases through clinically relevant information may be useful for diagnosis or treatment. METHODS: A variety of pulmonary fibrosis clinical gene expression omnibus (GEO) datasets were used to assess the association between CHST11-related manifestations and fibrosis. Multiple lung cancer-related databases, including The Cancer Genome Atlas, GEO datasets, UCSC Xena, GEPIA2, Cbioportal and ingenuity pathway analysis were used to evaluate the clinical correlation between CHST11 and lung cancer and potential molecular mechanisms. For drug repurposing prediction, the molecules that correlated with CHST11 were subjected to the LINCS L1000 algorithm. A variety of in vitro assays were performed to evaluate the in-silico models, including RNA and protein expression, proliferation, migration and invasion. RESULTS: Clinical analyses indicate that the levels of CHST11 are significantly elevated in cases of pulmonary-related diseases, including fibrosis and lung cancer. According to multiple lung cancer cohorts, CHST11 is the only member of the carbohydrate sulfotransferase family associated with overall survival for lung adenocarcinomas, and it is highly related to smoking-induced lung cancer patients. Based on the results of in vitro experiments, CHST11 expression contributes to tumor malignancy and promotes multiple fibrotic activators. Correlation-based ingenuity pathway analysis indicated that CHST11-related molecules contributed to pulmonary fibrosis or lung adenocarcinomas via similar upstream stimulators. Based on known molecular regulatory relationships, CHST11 has been associated with the regulation of TGF-ß and INFγ as important molecules contributing to fibrosis and cancer progression. Interestingly, WordCloud analysis revealed that CHST11-related molecules are involved in regulation primarily by integrin signaling, and these relationships were consistently reflected in the analysis of cell lines and the clinical correlation. A CHST11 signature-based drug repurposing analysis demonstrated that the CHST11/integrin axis could be targeted by AG-1478 (Tyrphostin AG 1478), brefeldin A, geldanamycin and importazole. CONCLUSIONS: This study provides the first demonstration that CHST11 may be used as a biomarker for pulmonary fibrosis or lung cancer, and the levels of CHST11 were increased by TGF-ß and INFγ. The molecular simulation analyses demonstrate that the CHST11/integrin axis is a potential therapeutic target for treating lung cancer.

Application of Metabolic Reprogramming to Cancer Imaging and Diagnosis.

Cellular metabolism governs the signaling that supports physiological mechanisms and homeostasis in an individual, including neuronal transmission, wound healing, and circadian clock manipulation. Various factors have been linked to abnormal metabolic reprogramming, including gene mutations, epigenetic modifications, altered protein epitopes, and their involvement in the development of disease, including cancer. The presence of multiple distinct hallmarks and the resulting cellular reprogramming process have gradually revealed that these metabolism-related molecules may be able to be used to track or prevent the progression of cancer. Consequently, translational medicines have been developed using metabolic substrates, precursors, and other products depending on their biochemical mechanism of action. It is important to note that these metabolic analogs can also be used for imaging and therapeutic purposes in addition to competing for metabolic functions. In particular, due to their isotopic labeling, these compounds may also be used to localize and visualize tumor cells after uptake. In this review, the current development status, applicability, and limitations of compounds targeting metabolic reprogramming are described, as well as the imaging platforms that are most suitable for each compound and the types of cancer to which they are most appropriate.

Magnetically guided theranostics: montmorillonite-based iron/platinum nanoparticles for enhancing in situ MRI contrast and hepatocellular carcinoma treatment.

In Asia, including Taiwan, malignant tumors such as Hepatocellular carcinoma (HCC) one of the liver cancer is the most diagnosed subtype. Magnetic resonance imaging (MRI) has been a typical diagnostic method for accurately diagnosing HCC. When it is difficult to demonstrate non-enhanced MRI of tumors, radiologists can use contrast agents (such as Gd3+, Fe3O4, or FePt) for T1-weighted and T2-weighted imaging remain in the liver for a long time to facilitate diagnosis via MRI. However, it is sometimes difficult for T2-weighted imaging to detect small tumor lesions because the liver tissue may absorb iron ions. This makes early cancer detection a challenging goal. This challenge has prompted current research to create novel nanocomposites for enhancing the noise-to-signal ratio of MRI. To develop a method that can more efficiently diagnose and simultaneously treat HCC during MRI examination, we designed a functionalized montmorillonite (MMT) material with a porous structure to benefit related drugs, such as mitoxantrone (MIT) delivery or as a carrier for the FePt nanoparticles (FePt NPs) to introduce cancer therapy. Multifunctional FePt@MMT can simultaneously visualize HCC by enhancing MRI signals, treating various diseases, and being used as an inducer of magnetic fluid hyperthermia (MFH). After loading the drug MIT, FePt@MMT-MIT provides both MFH treatment and chemotherapy in one nanosystem. These results ultimately prove that functionalized FePt@MMT-MIT could be integrated as a versatile drugs delivery system by combining with MRI, chemotheraeutic drugs, and magnetic guide targeting.

The Metabolism Reprogramming of microRNA Let-7-Mediated Glycolysis Contributes to Autophagy and Tumor Progression.

Cancer is usually a result of abnormal glucose uptake and imbalanced nutrient metabolization. The dysregulation of glucose metabolism, which controls the processes of glycolysis, gives rise to various physiological defects. Autophagy is one of the metabolic-related cellular functions and involves not only energy regeneration but also tumorigenesis. The dysregulation of autophagy impacts on the imbalance of metabolic homeostasis and leads to a variety of disorders. In particular, the microRNA (miRNA) Let-7 has been identified as related to glycolysis procedures such as tissue repair, stem cell-derived cardiomyocytes, and tumoral metastasis. In many cancers, the expression of glycolysis-related enzymes is correlated with Let-7, in which multiple enzymes are related to the regulation of the autophagy process. However, much recent research has not comprehensively investigated how Let-7 participates in glycolytic reprogramming or its links to autophagic regulations, mainly in tumor progression. Through an integrated literature review and omics-related profiling correlation, this review provides the possible linkage of the Let-7 network between glycolysis and autophagy, and its role in tumor progression.

RAB31 drives extracellular vesicle fusion and cancer-associated fibroblast formation leading to oxaliplatin resistance in colorectal cancer.

Epithelial-mesenchymal transition (EMT) is associated with tumorigenesis and drug resistance. The Rab superfamily of small G-proteins plays a role in regulating cell cytoskeleton and vesicle transport. However, it is not yet clear how the Rab family contributes to cancer progression by participating in EMT. By analysing various in silico datasets, we identified a statistically significant increase in RAB31 expression in the oxaliplatin-resistant group compared to that in the parental or other chemotherapy drug groups. Our findings highlight RAB31's powerful effect on colorectal cancer cell lines when compared with other family members. In a study that analysed multiple online meta-databases, RAB31 RNA levels were continually detected in colorectal tissue arrays. Additionally, RAB31 protein levels were correlated with various clinical parameters in clinical databases and were associated with negative prognoses for patients. RAB31 expression levels in all three probes were calculated using a computer algorithm and were found to be positively correlated with EMT scores. The expression of the epithelial-type marker CDH1 was suppressed in RAB31 overexpression models, whereas the expression of the mesenchymal-type markers SNAI1 and SNAI2 increased. Notably, RAB31-induced EMT and drug resistance are dependent on extracellular vesicle (EV) secretion. Interactome analysis confirmed that RAB31/AGR2 axis-mediated exocytosis was responsible for maintaining colorectal cell resistance to oxaliplatin. Our study concluded that RAB31 alters the sensitivity of oxaliplatin, a supplementary chemotherapy approach, and is an independent prognostic factor that can be used in the treatment of colorectal cancer.

Binding of interleukin-1 receptor antagonist to cholinergic receptor muscarinic 4 promotes immunosuppression and neuroendocrine differentiation in prostate cancer.

The tumor microenvironment (TME) of prostate cancer (PCa) is characterized by high levels of immunosuppressive molecules, including cytokines and chemokines. This creates a hostile immune landscape that impedes effective immune responses. The interleukin-1 (IL-1) receptor antagonist (IL1RN), a key anti-inflammatory molecule, plays a significant role in suppressing IL-1-related immune and inflammatory responses. Our research investigates the oncogenic role of IL1RN in PCa, particularly its interactions with muscarinic acetylcholine receptor 4 (CHRM4), and its involvement in driving immunosuppressive pathways and M2-like macrophage polarization within the PCa TME. We demonstrate that following androgen deprivation therapy (ADT), the IL1RN-CHRM4 interaction in PCa activates the MAPK/AKT signaling pathway. This activation upregulates the transcription factors E2F1 and MYCN, stimulating IL1RN production and creating a positive feedback loop that increases CHRM4 abundance in both PCa cells and M2-like macrophages. This ADT-driven IL1RN/CHRM4 axis significantly enhances immune checkpoint markers associated with neuroendocrine differentiation and treatment-resistant outcomes. Higher serum IL1RN levels are associated with increased disease aggressiveness and M2-like macrophage markers in advanced PCa patients. Additionally, elevated IL1RN levels correlate with better clinical outcomes following immunotherapy. Clinical correlations between IL1RN and CHRM4 expression in advanced PCa patients and neuroendocrine PCa organoid models highlight their potential as therapeutic targets. Our data suggest that targeting the IL1RN/CHRM4 signaling could be a promising strategy for managing PCa progression and enhancing treatment responses.

Glucose transporter 4: Insulin response mastermind, glycolysis catalyst and treatment direction for cancer progression.

The glucose transporter family (GLUT) consists of fourteen members. It is responsible for glucose homeostasis and glucose transport from the extracellular space to the cell cytoplasm to further cascade catalysis. GLUT proteins are encoded by the solute carrier family 2 (SLC2) genes and are members of the major facilitator superfamily of membrane transporters. Moreover, different GLUTs also have their transporter kinetics and distribution, so each GLUT member has its uniqueness and importance to play essential roles in human physiology. Evidence from many studies in the field of diabetes showed that GLUT4 travels between the plasma membrane and intracellular vesicles (GLUT4-storage vesicles, GSVs) and that the PI3K/Akt pathway regulates this activity in an insulin-dependent manner or by the AMPK pathway in response to muscle contraction. Moreover, some published results also pointed out that GLUT4 mediates insulin-dependent glucose uptake. Thus, dysfunction of GLUT4 can induce insulin resistance, metabolic reprogramming in diverse chronic diseases, inflammation, and cancer. In addition to the relationship between GLUT4 and insulin response, recent studies also referred to the potential upstream transcription factors that can bind to the promoter region of GLUT4 to regulating downstream signals. Combined all of the evidence, we conclude that GLUT4 has shown valuable unknown functions and is of clinical significance in cancers, which deserves our in-depth discussion and design compounds by structure basis to achieve therapeutic effects. Thus, we intend to write up a most updated review manuscript to include the most recent and critical research findings elucidating how and why GLUT4 plays an essential role in carcinogenesis, which may have broad interests and impacts on this field.

Overexpression of synaptic vesicle protein Rab GTPase 3C promotes vesicular exocytosis and drug resistance in colorectal cancer cells.

Rab GTPase 3C (RAB3C) is a peripheral membrane protein that is involved in membrane trafficking (vesicle formation) and cell movement. Recently, researchers have noted the exocytosis of RAB proteins, and their dysregulation is correlated with drug resistance and the altered tumor microenvironment in tumorigenesis. However, the molecular mechanisms of exocytotic RABs in the carcinogenicity of colorectal cancer (CRC) remain unknown. Researchers have used various in silico datasets to evaluate the expression profiles of RAB family members. We confirmed that RAB3C plays a key role in CRC progression. Its overexpression promotes exocytosis and is related to the resistance to several chemotherapeutic drugs. We established a proteomic dataset based on RAB3C, and found that dystrophin is one of the proteins that is upregulated with the overexpression of RAB3C. According to our results, RAB3C-induced dystrophin expression promotes vesicle formation and packaging. A connectivity map predicted that the cannabinoid receptor 2 (CB2) agonists reverse RAB3C-associated drug resistance, and that these agonists have synergistic effects when combined with standard chemotherapy regimens. Moreover, we found high dystrophin expression levels in CRC patients with poor survival outcomes. A combination of the dystrophin and RAB3C expression profiles can serve as an independent prognostic factor in CRC and is associated with several clinicopathological parameters. In addition, the RAB3C-dystrophin axis is positively correlated with the phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform (PIK3CA) genetic alterations in CRC patients. These findings can be used to provide novel combined therapeutic options for the treatment of CRC.

Amplification of oxidative stress by lipid surface-coated single-atom Au nanozymes for oral cancer photodynamic therapy.

Single-atom nanozymes (SANs) are the latest trend in biomaterials research and promote the application of single atoms in biological fields and the realization of protein catalysis in vivo with inorganic nanoparticles. Carbon quantum dots (CDs) have excellent biocompatibility and fluorescence properties as a substrate carrying a single atom. It is difficult to break through pure-phase single-atom materials with quantum dots as carriers. In addition, there is currently no related research in the single-atom field in the context of oral cancer, especially head and neck squamous cell carcinoma. This research developed a lipid surface-coated nanozyme combined with CDs, single-atomic gold, and modified lipid ligands (DSPE-PEG) with transferrin (Tf) to treat oral squamous cell carcinoma. The study results have demonstrated that surface-modified single-atom carbon quantum dots (m-SACDs) exhibit excellent therapeutic effects and enable in situ image tracking for diagnosing and treating head and neck squamous carcinoma (HNSCC).

The activation of EP300 by F11R leads to EMT and acts as a prognostic factor in triple-negative breast cancers.

Cancer progression is influenced by junctional adhesion molecule (JAM) family members. The relationship between JAM family members and different types of cancer was examined using The Cancer Genome Atlas dataset. mRNA levels of the F11R (F11 receptor) in tumours were inversely correlated to the expression of JAM-2 and JAM-3. This relationship was unique to breast cancer (BCa) and was associated with poor prognosis (p = 0.024, hazard ratio = 1.44 [1.05-1.99]). A 50-gene molecular signature (prediction analysis of microarray 50) was used to subtype BCa. F11R mRNA expression significantly increased in human epidermal growth factor receptor 2 (HER2)-enriched (p = 0.0035) and basal-like BCa tumours (p = 0.0005). We evaluated F11R protein levels in two different compositions of BCa subtype patient tissue array cohorts to determine the relationship between BCa subtype and prognosis. Immunohistochemistry staining revealed that a high F11R protein level was associated with poor overall survival (p < 0.001; Taipei Medical University [TMU] cohort, p < 0.001; Kaohsiung Veterans General Hospital [KVGH] cohort) or disease-free survival (p < 0.001 [TMU cohort], p = 0.034 [KVGH cohort]) in patients with BCa. Comparison of F11R levels in different subtypes revealed the association of poor prognosis with high levels of F11R among luminal (p < 0.001 [TMU cohort], p = 0.027 [KVGH cohort]), HER2 positive (p = 0.018 [TMU cohort], p = 0.037 [KVGH cohort]), and triple-negative (p = 0.013 [TMU cohort], p = 0.037 [KVGH cohort]) BCa. F11R-based RNA microarray analysis and Ingenuity Pathway Analysis were successful in profiling the detailed gene ontology of triple-negative BCa cells regulated by F11R. The EP300 transcription factor was highly correlated with F11R in BCa (R = 0.51, p < 0.001). By analysing these F11R-affected molecules with the L1000CDs datasets, we were able to predict some repurposing drugs for potential application in F11R-positive BCa treatment.

CHRM4/AKT/MYCN upregulates interferon alpha-17 in the tumor microenvironment to promote neuroendocrine differentiation of prostate cancer.

Current treatment options for prostate cancer focus on targeting androgen receptor (AR) signaling. Inhibiting effects of AR may activate neuroendocrine differentiation and lineage plasticity pathways, thereby promoting the development of neuroendocrine prostate cancer (NEPC). Understanding the regulatory mechanisms of AR has important clinical implications for this most aggressive type of prostate cancer. Here, we demonstrated the tumor-suppressive role of the AR and found that activated AR could directly bind to the regulatory sequence of muscarinic acetylcholine receptor 4 (CHRM4) and downregulate its expression. CHRM4 was highly expressed in prostate cancer cells after androgen-deprivation therapy (ADT). CHRM4 overexpression may drive neuroendocrine differentiation of prostate cancer cells and is associated with immunosuppressive cytokine responses in the tumor microenvironment (TME) of prostate cancer. Mechanistically, CHRM4-driven AKT/MYCN signaling upregulated the interferon alpha 17 (IFNA17) cytokine in the prostate cancer TME after ADT. IFNA17 mediates a feedback mechanism in the TME by activating the CHRM4/AKT/MYCN signaling-driven immune checkpoint pathway and neuroendocrine differentiation of prostate cancer cells. We explored the therapeutic efficacy of targeting CHRM4 as a potential treatment for NEPC and evaluated IFNA17 secretion in the TME as a possible predictive prognostic biomarker for NEPC.

The role of fructose 1,6-bisphosphate-mediated glycolysis/gluconeogenesis genes in cancer prognosis.

Metabolic reprogramming and elevated glycolysis levels are associated with tumor progression. However, despite cancer cells selectively inhibiting or expressing certain metabolic enzymes, it is unclear whether differences in gene profiles influence patient outcomes. Therefore, identifying the differences in enzyme action may facilitate discovery of gene ontology variations to characterize tumors. Fructose-1,6-bisphosphate (F-1,6-BP) is an important intermediate in glucose metabolism, particularly in cancer. Gluconeogenesis and glycolysis require fructose-1,6-bisphosphonates 1 (FBP1) and fructose-bisphosphate aldolase A (ALDOA), which participate in F-1,6-BP conversion. Increased expression of ALDOA and decreased expression of FBP1 are associated with the progression of various forms of cancer in humans. However, the exact molecular mechanism by which ALDOA and FBP1 are involved in the switching of F-1,6-BP is not yet known. As a result of their pancancer pattern, the relationship between ALDOA and FBP1 in patient prognosis is reversed, particularly in lung adenocarcinoma (LUAD) and liver hepatocellular carcinoma (LIHC). Using The Cancer Genome Atlas (TCGA), we observed that FBP1 expression was low in patients with LUAD and LIHC tumors, which was distinct from ALDOA. A similar trend was observed in the analysis of Cancer Cell Line Encyclopedia (CCLE) datasets. By dissecting downstream networks and possible upstream regulators, using ALDOA and FBP1 as the core, we identified common signatures and interaction events regulated by ALDOA and FBP1. Notably, the identified effectors dominated by ALDOA or FBP1 were distributed in opposite patterns and can be considered independent prognostic indicators for patients with LUAD and LIHC. Therefore, uncovering the effectors between ALDOA and FBP1 will lead to novel therapeutic strategies for cancer patients.

Ultrasound and Nanomedicine for Cancer-Targeted Drug Delivery: Screening, Cellular Mechanisms and Therapeutic Opportunities.

Cancer is a disease characterized by abnormal cell growth. According to a report published by the World Health Organization (WHO), cancer is the second leading cause of death globally, responsible for an estimated 9.6 million deaths in 2018. It should be noted that ultrasound is already widely used as a diagnostic procedure for detecting tumorigenesis. In addition, ultrasound energy can also be utilized effectively for treating cancer. By filling the interior of lipospheres with gas molecules, these particles can serve both as contrast agents for ultrasonic imaging and as delivery systems for drugs such as microbubbles and nanobubbles. Therefore, this review aims to describe the nanoparticle-assisted drug delivery system and how it can enhance image analysis and biomedicine. The formation characteristics of nanoparticles indicate that they will accumulate at the tumor site upon ultrasonic imaging, in accordance with their modification characteristics. As a result of changing the accumulation of materials, it is possible to examine the results by comparing images of other tumor cell lines. It is also possible to investigate ultrasound images for evidence of cellular effects. In combination with a precision ultrasound imaging system, drug-carrying lipospheres can precisely track tumor tissue and deliver drugs to tumor cells to enhance the ability of this nanocomposite to treat cancer.

Iron-Based Ceramic Composite Nanomaterials for Magnetic Fluid Hyperthermia and Drug Delivery.

Because of the unique physicochemical properties of magnetic iron-based nanoparticles, such as superparamagnetism, high saturation magnetization, and high effective surface area, they have been applied in biomedical fields such as diagnostic imaging, disease treatment, and biochemical separation. Iron-based nanoparticles have been used in magnetic resonance imaging (MRI) to produce clearer and more detailed images, and they have therapeutic applications in magnetic fluid hyperthermia (MFH). In recent years, researchers have used clay minerals, such as ceramic materials with iron-based nanoparticles, to construct nanocomposite materials with enhanced saturation, magnetization, and thermal effects. Owing to their unique structure and large specific surface area, iron-based nanoparticles can be homogenized by adding different proportions of ceramic minerals before and after modification to enhance saturation magnetization. In this review, we assess the potential to improve the magnetic properties of iron-based nanoparticles and in the preparation of multifunctional composite materials through their combination with ceramic materials. We demonstrate the potential of ferromagnetic enhancement and multifunctional composite materials for MRI diagnosis, drug delivery, MFH therapy, and cellular imaging applications.

Fascin-1: Updated biological functions and therapeutic implications in cancer biology.

Filopodia are cellular protrusions that respond to a variety of stimuli. Filopodia are formed when actin is bound to the protein Fascin, which may play a crucial role in cellular interactions and motility during cancer metastasis. Significantly, the noncanonical features of Fascin-1 are gradually being clarified, including the related molecular network contributing to metabolic reprogramming, chemotherapy resistance, stemness ac-tivity, and tumor microenvironment events. However, the relationship between biological characteristics and pathological features to identify effective therapeutic strategies needs to be studied further. The pur-pose of this review article is to provide a broad overview of the latest molecular networks and multiomics research regarding fascins and cancer. It also highlights their direct and indirect effects on available cancer treatments. With this multidisciplinary approach, researchers and clinicians can gain the most relevant in-formation on the function of fascins in cancer progression, which may facilitate clinical applications in the future.

Regorafenib inhibits epithelial-mesenchymal transition and suppresses cholangiocarcinoma metastasis via YAP1-AREG axis.

Cholangiocarcinoma (CCA) is a subtype of bile duct cancer usually diagnosed late with a low survival rate and no satisfactorily systemic treatment. Recently, regorafenib has been accepted as a second-line treatment for CCA patients. In this study, we investigated the potential signal transduction pathways mediated by regorafenib. We established a transcriptomic database for regorafenib-treated CCA cells using expression microarray chips. Our data indicate that regorafenib inhibits yes-associated protein 1 (YAP1) activity in various CCA cells. In addition, we demonstrated that YAP1 regulates epithelial-mesenchymal transition (EMT)-related genes, including E-cadherin and SNAI2. We further examined YAP1 activity, phosphorylation status, and expression levels of YAP1 downstream target genes in the regorafenib model. We found that regorafenib dramatically suppressed these events in CCA cells. Moreover, in vivo results revealed that regorafenib could significantly inhibit lung foci formation and tumorigenicity. Most importantly, regorafenib and amphiregulin (AREG) neutralize antibody exhibited synergistic effects against CCA cells. In a clinical setting, patients with high YAP1 and EMT expression had a worse survival rate than patients with low YAP1, and EMT expression did. In addition, we found that YAP1 upregulated the downstream target amphiregulin in CCA. Our findings suggest that AREG neutralizing antibody antibodies combined with regorafenib can reverse the CCA metastatic phenotype and EMT in vitro and in vivo. These findings provide novel therapeutic strategies to combat the metastasis of CCA.