Radiation Sensitivity Research Articles

Irisquinone's Anti-cancer Potential: Targeting TrxR to Trigger ROS-mediated Apoptosis and Pyroptosis.

Irisquinone, an important compound extracted from Semen Irisis, has been used clinically as a radiotherapy sensitizer for lung, oesophageal, head and neck, breast and leukemia cancers. However, the mechanism by which it acts against cancer is still unclear. The present study aims to investigate the anti-tumor activity and mechanism of Irisquinone. The effect of Irisquinone on cell viability and proliferation was evaluated using the CCK-8 assay. Fluorescence probe (Fast-TRFS) and DTNB assay were used to observe the inhibitory effect of Irisquinone on both intracellular and extracellular thioredoxin reductase (TrxR). The level of reactive oxygen species (ROS) in tumour cells was assessed using the DCFH-DA probe. Annexin V-FITC/PI, staining and microscopy experiments, were used to examine the apoptosis and pyroptosis. Western blotting analyses confirmed that Irisquinone induced apoptosis and pyroptosis in cancer cells by inhibiting TrxR to increase ROS generation. Our research has shown that Irisquinone has anti-proliferative effects on several cancer cell lines while having low toxicity to normal cells. The amount of ROS induced by inhibition of TrxR activated the BAX (proapoptotic protein) and caspase-1(the pro-pyroptotic protein) to induce apoptosis and pyroptosis. Irisquinone showed anticancer activity through inhibiting TrxR. These results suggested that Irisquinone will be developed to be an anti-tumor drug possibility.

RNF7-Mediated ROS Targets Malignant Phenotype and Radiotherapy Sensitivity in Glioma With Different IDH1 Genotypes.

RNF7 (Ring Finger Protein 7) is a key component of CRLs (Cullin-RING-type E3 ubiquitin ligases) and has been found to possess intrinsic anti-ROS capabilities. Aberrant expression of RNF7 has been observed in various tumor types and is known to significantly influence tumor initiation and progression. However, the specific role of RNF7 in glioblastoma remains unclear. IDH (isocitrate dehydrogenase) mutations, which induce metabolic reprogramming and result in notable heterogeneity among glioma with different IDH genotypes. Through analysis of public glioma databases, we identified a high expression of RNF7 in glioma and its correlation with patient prognosis. Moreover, we observed variations in RNF7 expression and its association with patient outcomes under different treatment modalities among different IDH genotypes. In this study, we demonstrated the critical role of RNF7 in the malignant phenotype of IDH1-mutant glioma and its contribution to radiation resistance. Subsequent functional enrichment analysis of RNF7 in glioma, coupled with validation through cellular experiments, confirmed its significant involvement in maintaining redox balance. Our findings suggest that RNF7 exerts a buffering effect against radiation-induced oxidative stress and counterbalances the redox stress induced by IDH1 mutation through its anti-ROS activity. Additionally, our follow-up investigations revealed that the upregulation of RNF7 after radiation exposure and in IDH1-mutant glioma cells is induced by ROS. Collectively, our study underscores the potential of RNF7 as a molecular biomarker in glioma. Elevated RNF7 expression often indicates a heightened metabolic resilience in glioma, leading to resistance against radiotherapy.

Concurrent Amplification of Ferroptosis and Immune System Activation Via Nanomedicine-Mediated Radiosensitization for Triple-Negative Breast Cancer Therapy.

Radiation therapy (RT) is one of the core therapies for current cancer management. However, the emergence of radioresistance has become a major cause of radiotherapy failure and disease progression. Therefore, overcoming radioresistance to achieve highly effective treatment for refractory tumors is significant yet challenging. Here, pH-responsive DSPE-PEoz modified hollow Bi2Se3-RSL3/diABZi (DP-HBN/RA) nanomedicine is designed as a radiation sensitizer for efficient treatment of triple-negative breast cancer by simultaneously amplifying ferroptosis and immune system activation. DP-HBN/RA can efficiently concentrate X-ray radiation energy inside the tumor, thereby promoting precise ionizing radiation exposure in tumor cells to produce large amounts of reactive oxygen species (ROS), leading to lipid peroxidation-induced ferroptosis. Meanwhile, ferroptotic cell death is intensified through the inactivation of GPX4 by RSL3 released from DP-HBN/RA to acidic conditions in the tumor microenvironment. Additionally, DP-HBN/RA enhances RT efficacy to exacerbate unrepairable DNA damage and release DNA fragments that activate the cGAS-STING signal pathway, evoking a systematic immune response. Ingeniously, the released diABZi reinforces cGAS-STING activation to boost the immunology antitumor effect. This work links the induction of ferroptosis and the initiation of systematic immune response to achieve highly effective tumor suppression, which opens up new avenues for future treatments of refractory tumors.

Scintillating Glass Fiber Arrays Enable Remote Radiation Detection and Pixelated Imaging.

The emerging metal halide perovskites are challenging the traditional scintillators in the field of radiation detection and radiography. However, they lack the capability for remote and real-time radiation monitoring and imaging in confined and hostile conditions. To address this issue, details on an inorganic scintillating glass fiber incorporating perovskite quantum dots (QDs) as highly efficient pixelated radiation emitters are reported, while the glass fibers themselves serve at the same time as low-loss waveguides, enabling long-distance and underwater X-ray detection. The multi-color emissions and controllable radiation sensitivities endow CsPbX3 (X = Cl, Br, I) QD scintillating glass fibers with the potential as wearable and visualized radiation indicators. Furthermore, these scintillating glass fibers can be regularly arranged into a fiber array plate with a thickness of 7.5mm to enhance X-ray absorption for X-ray imaging. Leveraging the light-guiding character of glass fibers, a 5 × 5 fiber array with fiber lengths up to 11cm has demonstrated the potential of remote pixelated X-ray imaging. This study offers a novel platform for the development of remote detectors and imagers for X-ray radiation.

Synthesis and Characterization of Gold-Nanoparticle-Loaded Block Copolymer Vectors for Biomedical Applications: A Multivariate Analysis.

Gold nanoparticles (GNPs) encapsulated in amphiphilic block copolymers are a promising system for numerous biomedical applications, although critical information on the effects of various preparation variables on the structure and properties of this unique type of nanomaterial is currently missing from the literature. In this research, we synthesized GNPs functionalized with thiol-terminated polycaprolactone (PCL-GNPs) before encapsulating them into poly(ε-caprolactone)-b-poly(ethylene glycol) (PCL-b-PEG) micellar nanoparticles via nanoprecipitation to yield GNP-loaded polymeric nanoparticles (GNP-PNPs). We explored the role of different manufacturing variables (water volume, PCL-b-PEG to PCL-GNP ratio, and PEG block length) on the sizes, morphologies, GNP occupancies, colloidal gold concentrations, and time stability of GNP-PNPs. Despite our motivation to increase colloidal gold concentrations for K-edge CT imaging applications, there was only moderate variation in the concentration of colloidal gold (cAu = ∼100-150 μg/mL) over the range of investigated experimental variables; however, postformulation exposure to compressed air flow provided samples with increased gold concentrations and CT contrast above the visual threshold in imaging phantoms. The range of formulation variables also had only a weak effect on mean effective hydrodynamic diameters (dh,eff = ∼150 nm). Statistical analysis of TEM images revealed that the mean number of GNPs within GNP-PNP vectors smaller than 50 nm, Zave,d<50nm, is generally higher for preparations involving PCL-b-PEG with the shorter of the two different PEG block lengths. Preparations with the shorter PEG block length copolymer were also found to produce GNP-PNP colloids with greater time stability in dh,eff and cAu. Consistent with our previous study using MB-MDA-231 cells, we found increased gold uptake in MCF-7 cells with increasing Zave,d<50nm. This study provides a roadmap for optimizing important figures of merit for existing biomedical applications, including CT imaging and radiotherapy sensitization, and for developing new diagnostic and therapeutic strategies using GNP-PNPs.

Asymmetrically PEGylated and amphipathic heptamethine indocyanine dyes potentiate radiotherapy of renal cell carcinoma via mitochondrial targeting

Enhancing the sensitivity of radiotherapy (RT) towards renal cell carcinoma (RCC) remains a challenge because RCC is a radioresistant tumor. In this work, we design and report asymmetrically Polyethylene Glycol (PEG)ylated and amphipathic heptamethine indocyanine dyes for efficient radiosensitization of RCC treatment. They were synthesized by modifying different lengths of PEG chains as hydrophilic moieties on one N-alkyl chain of a mitochondria-targeting heptamethine indocyanine dye (IR-808), and a radiosensitizer 2-nitroimidazole (NM) as a hydrophobic moiety on another N-alkyl chain. The PEG modification significantly improved water solubility, decreased the intermolecular π–π large aggregates, thereby enhanced renal excretion. The asymmetrical and amphipathic modification enhanced the preferential accumulation in renal tumors through self-assembly into small-size nanoparticles in aqueous environment. Radiosensitization was further improved by preferential accumulation in renal tumor cells and their mitochondria as mitochondria play a crucial role in rapid cancer cell growth, metastasis, and RT resistance. Additionally, the modification also increased the abilities of fluorescence emission and photostability, which is meaningful for imaging-guided precise RCC RT. Therefore, our findings may present a theranostic radiosensitizer for renal tumor-targeted imaging and radiosensitization.Graphical

LAT4 drives temozolomide induced radiotherapy resistance in glioblastoma by enhancing mTOR pathway activation

BackgroundGlioblastoma multiforme (GBM) represents the most prevalent form of primary malignant tumor within the central nervous system. The emergence of resistance to radiotherapy and chemotherapy represents a significant impediment to advancements in glioma treatment.MethodsWe established temozolomide (TMZ)-resistant GBM cell lines by chronically exposing U87MG cell lines to TMZ, and dimethyl sulfoxide (DMSO) was used as placebo control. In vivo and in vitro experiments verified the resistance of resistant cells to chemotherapy and radiotherapy. LAT4 was identified by transcriptomics to be associated with GBM treatment resistance and relapse. The relationship between LAT4 and mTOR pathway activity was also analyzed. Finally, the effect of BCH (LAT inhibitor) combined with radiotherapy on GBM prognosis was verified in vivo.ResultsWe have first confirmed that TMZ not only induces resistance to chemotherapy in GBM cells but also enhances their resistance to radiotherapy, which is a significant finding in the process of building TMZ-resistant U87MG GBM cell lines. We then performed comprehensive transcriptomic analysis and identified amino acid metabolism as a potential key factor in radiotherapy resistance. Specifically, we confirmed that the upregulation of LAT4 following chemotherapy enhances leucine metabolism within tumors in vitro and in vivo, thereby modulating the mechanistic target of mTOR pathway and leading to radiotherapy resistance. Of note, the application of inhibitors targeting leucine metabolism was shown to restore the sensitivity of these cells to radiotherapy, highlighting a potential therapeutic strategy for overcoming resistance in GBM.ConclusionsOur study links tumor sensitivity to chemotherapy and radiotherapy and highlights the critical role of LAT4 in activating the mTOR pathway and GBM radiotherapy resistance. It suggests ways to improve radiotherapy sensitivity to GBM.

Enhancing Chordoma Radiotherapy: Ta@PVP Nanoparticles as Potent Radiosensitizers.

Surgical resection and high-dose radiotherapy constitute the standard therapeutic approaches for chordoma. However, the efficacy of radiotherapy is often compromised by the tumor microenvironment's hypoxic conditions, which confer radiation resistance, and by the potential damage to adjacent spinal cord and neural structures from elevated radiation doses. To address these challenges, we employed high biocompatible poly(vinylpyrrolidone)-modified tantalum nanoparticles (Ta@PVP NPs) as a potent radiosensitizer to augment the radiotherapy sensitivity of chordoma. Upon exposure to X-ray irradiation, Ta@PVP NPs demonstrated the capability to efficiently deposit X-ray radiation energy within the tumor microenvironment, subsequently generating reactive oxygen species (ROS) that induce oxidative stress in the tumor. Both in vitro and in vivo experiments revealed that Ta@PVP NPs significantly enhanced the cytotoxic effects of X-ray, thereby markedly inhibiting the proliferation of chordoma cells and impeding tumor growth. This study explored the radiosensitization potential of Ta@PVP NPs in the context of chordoma, highlighting the application of radiosensitizers as a promising strategy to augment the efficacy of chordoma radiotherapy.

Hydrogen-Generating Magnesium Alloy Seed Strand Sensitizes Solid Tumors to Iodine-125 Brachytherapy.

Radioactive iodine-125 (125I) seed implantation, a brachytherapy technique, effectively kills tumor cells via X-rays and gamma rays, serving as an alternative therapeutic option following the failure of frontline treatments for various solid tumors. However, tumor radioresistance limits its efficacy. Hydrogen gas has anticancer properties and can enhance the efficacy of immunotherapy. However, its role in radiotherapy sensitization has rarely been reported. Many current hydrogen delivery methods involve hydrogen-generating nanomaterials, such as magnesium-based nanomaterials. This study introduces an AZ31 magnesium alloy 125I seed strand (termed AMASS) with pH-dependent slow-release hydrogen characteristics and excellent mechanical properties. AMASS can be implanted into tumors via minimally invasive surgery, releasing hydrogen around the 125I seeds. In vitro experiments showed that hydrogen from AMASS degradation significantly inhibited tumor proliferation, increased apoptosis, disrupted redox homeostasis and mitochondrial membrane potential, reduced adenosine triphosphate levels, and induced DNA damage due to 125I radiation. In mouse xenograft and rabbit liver tumor models, hydrogen from AMASS showed superior therapeutic effects compared with 125I seeds alone, with no noticeable side effects. In addition, AMASS has a uniform radiation dose distribution and simple implantation. Therefore, hydrogen from AMASS enhanced 125I seed efficacy, supporting the further promotion and application of 125I seed implantation in cancer therapy.

Golden era of radiosensitizers.

The past 30 years have brought undeniable progress in medicine, biology, physics, and research. Knowledge of the nature of the human body, diseases, and disorders has been constantly improving, and the same is true regarding their treatment and diagnosis. One of the greatest advances in recent years has been the introduction of nanoparticles (NPs) into medicine. NPs refer to a material at a nanometer scale (0.1-100 nm) with features (specific physical, chemical, and biological properties) that are broadly and increasingly used in the medical field. Their applications in cancer treatment and radiotherapy seem particularly attractive. In this field, inorganic/metal NPs with high atomic number Z have been employed mainly due to their ability to enhance ionizing radiation's photoelectric and Compton effects and thereby increase conventional radiation therapy's efficacy. The improvement NPs enable relates to their enhanced permeation ability and longer retention effect in tumor cells, capacity to reduce toxicity of commercially available cancer drugs through advanced NPs drug delivery systems, radiation sensitizers of tumors, or enhancers of radiation doses to tumors. Advanced options according to size, core, and surface modification allow even such multimodal approaches in therapy as nanotheranostics or combined treatments. The current state of knowledge emphasizes the role of gold nanoparticles (AuNPs) in sensitizing tumors to radiation. We have reviewed AuNPs and their radiosensitizing power during radiation treatment. Our results are divided into groups based on AuNPs' surface modification and/or core structure design. This study provides a complete summary of the in vivo sensitizing effect of AuNPs, surface-modified AuNPs, and AuNPs combined with different elements, providing evidence for further successful veterinarian and clinical implementation.

A High-Throughput Neurosphere-Based Colony Formation Assay to Test Drug and Radiation Sensitivity of Different Patient-Derived Glioblastoma Lines.

The gold standard assay for radiation response is the clonogenic assay, a normalized colony formation assay (CFA) that can capture a broad range of radiation-induced cell death mechanisms. Traditionally, this assay relies on two-dimensional (2D) cell culture conditions with colonies counted by fixing and staining protocols. While some groups have converted these to three-dimensional (3D) conditions, these models still utilize 2D-like media compositions containing serum that are incompatible with stem-like cell models such as brain tumor initiating cells (BTICs) that form self-aggregating spheroids in neural stem cell media. BTICs are the preferred patient-derived model system for studying glioblastoma (GBM) as they tend to better retain molecular and phenotypic characteristics of the original tumor tissue. As such, it is important that preclinical radiation studies should be adapted to BTIC conditions. In this study, we describe a series of experimental approaches for performing CFA experiments with BTIC cultures. Our results indicate that serum-free clonogenic assays are feasible for combination drug and radiation testing and may better facilitate translatability of preclinical findings.

Radiation source detection for the accurate location of lymph node metastases using robotic forceps-type coincidence radiation detector.

We have developed a forceps-type coincidence radiation detector for supporting lymph node dissection in esophageal cancer treatment. For precise detecting, this study aims to measure the 2D point-spread function of the detector at three difference tip angles, to devise a method to determine the position of a point source using the 2D point-spread function. The 2D sensitivity distribution on the surface of the detector was investigated to assess sensitivity variation caused by differences in the relative positions of the detector and radiation source. Based on the results, we identified the peak sensitivity value and proposed a detection method using this value. We evaluated the effectiveness of the proposed method by detecting radiation source location using this simulated distribution. From the radiation sensitivity distribution measurements, we observed a gradual decrease in radiation detection sensitivity from the center toward the edges of the detector surface. Additionally, we verified that the peak sensitivity value was attainable. Through the basic verification of the detection method, we confirmed that the radiation source location could be detected within a maximum error of 1.4mm. We developed a peak value search method aimed at mitigating sensitivity variations by leveraging the sensitivity distribution across the detector surface. The proposed device is thought to be able to quantitatively evaluate the desired target assuming that the field of view could be limited to the area clamped by the detector. As a next research step, more precise search methods should be verified in an environment resembling the one of the target clinical uses.

The Combined Effect of Hypoxia Activation and Radiosensitization by a Multifunctional Nanoplatform System Enhances the Therapeutic Efficacy of Chemoradiotherapy in Pancreatic Cancer

BackgroundPancreatic cancer is a highly malignant tumor, which is still a major global health problem. Chemotherapy and radiotherapy are regularly used in adjuvant therapy for pancreatic cancer but their therapeutic efficacy is limited. MethodsIn the present study, nanoparticle（MSN-AuNPs） was used as a drug carrier loaded with tirapazamine(TPZ) and hyaluronic acid (HA) to synthesize a multifunctional nanoplatform HA@TPZ-MSN-AuNPs (HTMA) for hypoxia activation and radiotherapy sensitization, which can be combined with radiotherapy therapy and synergistically enhance the therapeutic effect in pancreatic cancer. The anti-tumor performance of the nano platform was verified by in vivo and in vitro experiments. ResultFirst, the HA@TPZ-MSN-AuNPs (HTMA) was successfully synthesized. Drug release experiments showed that acidic environment and hyaluronidase promoted drug release in the nanoplatform. In vitro experiments, CCK-8, live-dead staining, clonal formation assay and flow cytometry confirmed the combined anti-tumor effect of hypoxia activation and radiotherapy sensitization with HTMA. In the drug uptake experiment, the nanoplatform showed the function of targeting and binding pancreatic cancer cells. In vivo, HTMA demonstrated good antitumor properties and good biocompatibility. ConclusionsThe nanoplatform had a good targeting effect and synergistic anti-tumor effect. The combination of hypoxia activation and radiotherapy sensitization is a promising strategy for the treatment of pancreatic cancer.

Targeting ATM enhances radiation sensitivity of colorectal cancer by potentiating radiation-induced cell death and antitumor immunity.

The efficacy of radiotherapy in colorectal cancer (CRC) is often limited by radiation resistance. Ataxia telangiectasia mutated (ATM) is well known for its role in repairing double-strand DNA breaks within the DNA damage response (DDR) pathway. However, whether ATM mediates other mechanisms contributing to radiation resistance remains insufficiently investigated. This study investigates how targeting ATM enhances CRC radiation sensitivity and evaluates combination strategies to improve radiotherapy outcomes. Clinical specimens were analyzed to correlate ATM activation with radiotherapy response. Functional assays, including EdU, cell viability, clonogenic survival, and apoptosis assays, were used to assess the impact of ATM inhibition on radiation sensitivity. Mechanistic insights were gained through RNA-seq, RT-qPCR, western blotting, ELISA, immunofluorescence, flow cytometry, ChIP-qPCR, and co-immunoprecipitation. In vivo efficacy was evaluated using subcutaneous tumor models in nude, BALB/c, and C57BL/6J mice. High ATM phosphorylation levels correlated with poor radiotherapy response in CRC patients. ATM inhibition enhanced radiation sensitivity in both in vitro and in vivo models. Mechanistically, ATM inhibition increased radiation-induced ROS accumulation and mitochondrial damage, leading to the release of mitochondrial DNA (mtDNA) into the cytosol and activation of the STING-type I interferon pathway. This enhanced CD8+ T cell infiltration and boosted antitumor immunity. Additionally, ATM inhibition partially alleviated the radiation-induced upregulation of PD-L1, likely through the ATM/NEMO/NF-κB pathway. Notably, triple therapy combining radiotherapy, an ATM inhibitor, and anti-PD-L1 achieved superior tumor control and remission in mouse models, including large, treatment-resistant tumors. Targeting ATM enhances radiation-induced tumor cell death and boosts antitumor immune responses, offering a promising strategy to overcome CRC radiation resistance. The synergy of radiotherapy, ATM inhibitior, and immune checkpoint blockade highlights a novel therapeutic approach for CRC management.

Overcoming Breast Cancer Treatment Resistance with Optimizing Sonodynamic Therapy and Radiation Sensitizers on lncRNA PVT1 and miR-1204 Expression.

Acoustic cavitation is a foundational mechanism in ultrasound therapy, primarily through inertial cavitation resulting from microbubble collapse. Sonodynamic therapy, with inertial acoustic cavitation threshold and low-dose radiation in the presence of sensitizers, may provide significant effects for cancer treatment, potentially overcoming resistance encountered with single therapies. MCF7 breast cancer cells were subjected to sonodynamic therapy either alone or combined with ionizing radiation, gold nanoparticles coated with apigenin, and methylene blue. Several parameters were evaluated, including reactive oxygen species (ROS) generation and colonization. Additionally, the investigation included assessing the long non-coding RNA (lncRNA) PTV1 with miRNA1204 and related genes using Real-Time PCR. Sonodynamic therapy at a mechanical index of 0.31 as acoustic cavitation threshold increased intracellular ROS. Combining sonodynamic therapy and 2Gy X-ray radiation with methylene blue and gold nanoparticles coated with apigenin significantly decreased plating efficiency (4.44±1.69), and survival fraction (2.75±1.98) compared with control (Ctrl.) (98.77±4.49) and (97.59± 2.94), respectively. This was associated with a marked increase in ROS with a mean fluorescence intensity of 20576.2 ± 4.6 (>4.5 times). The combined treatment also increased p53 expression and decreased the expression of PVT1, miR-1204, and related genes. Sonodynamic therapy in inertial acoustic cavitation threshold, combined with ionizing radiation in the presence of biocompatible nanoparticles, could enhance the therapeutic effects on the miR-1204, derived from lncRNA PVT1, that functions as an oncogenic microRNA in breast cancer. This approach has the potential to overcome treatment resistance encountered with single therapies.

Enhancing tumor radiotherapy sensitivity through metal nanomaterials: A comprehensive review

AbstractRadiotherapy (RT) plays a crucial role in tumor treatment and is an indispensable therapeutic approach. However, ionizing radiation often damages the normal tissues surrounding the tumor. Therefore, there is an urgent need for effective methods to improve the precision of RT. Nanotechnology has shown potential in enhancing the efficacy and safety of tumor RT. With the continuous development of multifunctional nanomaterials, various nanomaterials have been designed and investigated as radiation enhancers. Metallic nanomaterials are considered as promising radiosensitizers with potential for clinical translation. High atomic number (high‐Z) metal nanoparticles (NPs), such as gold and bismuth, have garnered increasing attention for their ability to enhance the radiation effect, as they can potentially improve RT outcomes. New nanomedicine strategies may help to advance RT. This paper concisely explains the radiation enhancement mechanisms of high‐Z metal NPs. It also enumerates several commonly studied high‐Z metallic nanomaterials used in tumor RT and discusses their potential clinical applications.

Enhancing radiotherapy in triple-negative breast cancer with hesperetin-induced ferroptosis via AURKA targeting nanocomposites

Triple-negative breast cancer (TNBC) is an aggressive cancer type that lacks targeted treatment options. Ferroptosis, a novel therapeutic strategy, induces cell death by disrupting the oxidative-reductive balance. Hesperetin, a potential TNBC therapeutic drug, has unidentified regulatory targets. The objective of this study was to explore the potential targets of hesperetin in TNBC and investigate whether the nanocomposites carrier hesperetin-loaded ferroptosis-inducing nanocomposites (HFPN), which activates ferroptosis, can enhance the anti-tumor efficacy of hesperetin. Bioinformatics methods were employed to screen hesperetin targets in TNBC, and a molecular docking model between hesperetin and the core target aurora kinase A (AURKA) was successfully constructed. The stability and anti-tumor activity of HFPN were validated in cell and mouse models, including tumor suppression and increased radiation sensitivity. These results suggest that HFPN can regulate the core target AURKA in TNBC, disrupt tumor oxidative-reductive balance, promote ferroptosis in tumor cells, and ultimately enhance the effectiveness of radiation therapy for TNBC.Graphical abstract

Innovations in radiotherapy for tongue squamous cell carcinoma

Radiotherapy sensitivity is associated with the prognosis of patients with tongue squamous cell carcinoma (TSCC). In the present study, we proposed to explore the specific mechanism of interventional radiology (IR) therapy for TSCC in vitro and in vivo. TSCC cells were treated with 6 Gy IR and tumor bearing mice were treated with 20 Gy × 1 IR. DIA quantitative proteomics along with bioinformatics analysis were conducted in TSCC cells to investigate differential proteins related to IR and relation of which involved in TMEM147 and SPHK1 was confirmed by immunoprecipitation. Cell proliferation, apoptosis, autophagy& autophagy flux along with calcium signaling pathway detection were performed in vitro and in vivo. Our results showed that IR induced increasing calcium levels accompanied by up-regulated TMEM147 and down-regulated SPHK1 along with enhancing autophagy together with apoptosis. The effect of calcium overloading induced by IR on autophagy and apoptosis was dependent on increasing TMEM147 and decreasing SPHK1. However, IR-induced autophagy and apoptosis tended to be independent of only increasing calcium levels when down-regulating TMEM147 or up-regulating SPHK1 expression in vitro and in vivo. Our study suggested that calcium-mediated TMEM147/SPHK1 may promote autophagy and apoptosis to improve radiotherapy sensitivity in TSCC.

CPT1A mediates radiation sensitivity in colorectal cancer

The prevalence and mortality rates of colorectal cancer (CRC) are increasing worldwide. Radiation resistance hinders radiotherapy, a standard treatment for advanced CRC, leading to local recurrence and metastasis. Elucidating the molecular mechanisms underlying radioresistance in CRC is critical to enhance therapeutic efficacy and patient outcomes. Bioinformatic analysis and tumour tissue examination were conducted to investigate the CPT1A mRNA and protein levels in CRC and their correlation with radiotherapy efficacy. Furthermore, lentiviral overexpression and CRISPR/Cas9 lentiviral vectors, along with in vitro and in vivo radiation experiments, were used to explore the effect of CPT1A on radiosensitivity. Additionally, transcriptomic sequencing, molecular biology experiments, and bioinformatic analyses were employed to elucidate the molecular mechanisms by which CPT1A regulates radiosensitivity. CPT1A was significantly downregulated in CRC and negatively correlated with responsiveness to neoadjuvant radiotherapy. Functional studies suggested that CPT1A mediates radiosensitivity, influencing reactive oxygen species (ROS) scavenging and DNA damage response. Transcriptomic and molecular analyses highlighted the involvement of the peroxisomal pathway. Mechanistic exploration revealed that CPT1A downregulates the FOXM1-SOD1/SOD2/CAT axis, moderating cellular ROS levels after irradiation and enhancing radiosensitivity. CPT1A downregulation contributes to radioresistance in CRC by augmenting the FOXM1-mediated antioxidant response. Thus, CPT1A is a potential biomarker of radiosensitivity and a novel target for overcoming radioresistance, offering a future direction to enhance CRC radiotherapy.

Efficacy of Gamma Irradiation in Eliminating Salmonella typhimurium Contamination in Seafood

Salmonella is a foodborne pathogen known to cause gastrointestinal disturbances. Contamination of seafood with Salmonella is a major public health concern, often occurring through cross-contamination. The natural habitat of Salmonella is the gastrointestinal tract of animals, including birds and humans. The current research study was carried out to investigate the gamma radiation sensitivity of Salmonella Typhimurium (NCIM 2501) in shrimp, squid, and clam samples. The decimal reduction dose (D10) values of Salmonella Typhimurium in saline and nutrient broth were 0.119 ± 0.004 kGy and 0.139 ± 0.0014 kGy, respectively. Seafood samples such as shrimp, squid, and clams were inoculated with Salmonella Typhimurium and exposed to gamma irradiation at doses of 0, 0.1, 0.2, 0.3, and 0.4 kGy to evaluate the effectiveness of irradiation in the complete elimination of Salmonella Typhimurium. The D10 values of Salmonella Typhimurium in shrimp, squid, and clam samples were found to be 0.182 ± 0.0007 kGy, 0.209 ± 0.0014 kGy, and 0.192 ± 0.004 kGy, respectively. Gamma radiation treatment at a dose of 5 kGy resulted in the complete reduction of 6.85 × 10⁸ CFU/g of Salmonella Typhimurium from shrimp, squid, and clam samples. Additionally, no recovery of Salmonella Typhimurium was observed in 5 kGy-treated shrimp, squid, and clam samples stored at 4°C for up to 12 days, even after enrichment and selective plating. The results of the study reveal that application of gamma irradiation is very effective to control Salmonella contamination in seafood without affecting sensory quality and ensures seafood safety.