Feedback loop between hypoxia and energy metabolic reprogramming aggravates the radioresistance of cancer cells.

Radiotherapy is one of the mainstream approaches for cancer treatment, although the clinical outcomes are limited due to the radioresistance of tumor cells. Hypoxia and metabolic reprogramming are the hallmarks of tumor initiation and progression and are closely linked to radioresistance. Inside a tumor, the rate of angiogenesis lags behind cell proliferation, and the underdevelopment and abnormal functions of blood vessels in some loci result in oxygen deficiency in cancer cells, i.e., hypoxia. This prevents radiation from effectively eliminating the hypoxic cancer cells. Cancer cells switch to glycolysis as the main source of energy, a phenomenon known as the Warburg effect, to sustain their rapid proliferation rates. Therefore, pathways involved in metabolic reprogramming and hypoxia-induced radioresistance are promising intervention targets for cancer treatment. In this review, we discussed the mechanisms and pathways underlying radioresistance due to hypoxia and metabolic reprogramming in detail, including DNA repair, role of cancer stem cells, oxidative stress relief, autophagy regulation, angiogenesis and immune escape. In addition, we proposed the existence of a feedback loop between energy metabolic reprogramming and hypoxia, which is associated with the development and exacerbation of radioresistance in tumors. Simultaneous blockade of this feedback loop and other tumor-specific targets can be an effective approach to overcome radioresistance of cancer cells. This comprehensive overview provides new insights into the mechanisms underlying tumor radiosensitivity and progression.

The association between the composite dietary antioxidant index and thyroid functionality among adults in the USA: NHANES 2007-2012.

Objective: Composite Dietary Antioxidant Index (CDAI) values serve as a summary of an individual's combined dietary antioxidant intake. Although specific antioxidants are known to reduce thyroid damage from oxidative stress, the relationship between the CDAI and thyroid function remains uncertain. The purpose of this study was thus to investigate this relationship in greater detail while focusing on a representative American adult population. Methods: A total of 6,860 subjects from the 2007-2012 NHANES cohort were included in this study. Associations between CDAI values and thyroid function were evaluated with weighted linear regression models and smoothed curve fitting. Subgroup analyses were also performed. Results: The weighted mean (SD) values for variables analyzed in this study included a CDAI of 0.13 (0.06), serum free T4 (FT4) levels of 0.80 (0.01) ng/dL, and serum total T4 (TT4) levels of 7.80 (0.03) ug/dL. Lower CDAI values were found to be associated with higher levels of FT4 and TT4 using both unadjusted and adjusted models that accounted for relevant confounders (adjusted model, FT4 ß = -0.003, p = 0.005; TT4 ß = -0.035, p < 0.001). This negative correlation persisted when CDAI was categorized into quartiles (FT4, p for trend = 0.014; TT4, p for trend = 0.003). Conclusion: These findings suggest that a diet rich in antioxidants, as reflected by higher CDAI scores, is associated with significant decreases in levels of free and total T4. Further analyses will be necessary to better clarify the underlying mechanisms behind these observations.

Efficacy and safety of fibrin sealant application in patients undergoing thyroidectomy: a systematic review and meta-analysis.

Various studies have focused on the application of fibrin sealants (FS) in thyroid surgery. Utilizing a meta-analysis, this systematic review analyzed the findings of recent randomized controlled trials on the safety and efficacy of FS in patients who underwent thyroidectomy. The Cochrane Library, Web of Science, Embase, PubMed, and Medline databases were searched for relevant studies, without any language restrictions. Seven randomized controlled trials were included in the originally identified 69 studies. Overall, 652 patients received FS during thyroid surgery; their outcomes were compared with those of conventionally treated patients. The primary outcomes were total volume of wound drainage, length of hospitalization, and operative time. Significant differences were observed in the total volume of wound drainage (mean deviation (MD): -29.75, 95% confidence interval (CI): -55.39 to -4.11, P = 0.02), length of hospitalization (MD: -0.84, 95% CI: -1.02 to -0.66, P < 0.00001), and surgery duration (MD: -7.60, 95% CI: -14.75 to -0.45, P = 0.04). Secondary outcomes were seroma and hypoparathyroidism development. The risk of hypoparathyroidism did not differ between the FS and conventional groups (I = 0%, relative risk = 1.31, P = 0.38). Analysis of "seroma formation that required invasive treatment" indicated that FS showed some benefit (I2 = 8%, relative risk 0.44, P = 0.15). Heterogeneity among the different trials limited their conclusions. The meta-analysis showed that although FS use did not significantly reduce seroma or hypoparathyroidism incidence in patients after thyroidectomy, it significantly reduced the total drainage volume, length of hospitalization, and duration of surgery.

Associations among thyroid hormone levels and mean corpuscular volume in adults in the US: A cross-sectional examination of the NHANES 2007-2012 dataset.

Mean corpuscular volume (MCV) is an important indicator used to determine the etiology of anemia and is associated with a variety of diseases. However, the link between thyroid function and MCV has yet to be clarified. This study was thus developed to assess relationships between thyroid function and MCV in a population of adults in the US. Results from the National Health and Nutrition Examination Survey study performed from 2007 to 2012 were used to conduct a cross-sectional analysis. Key thyroid-related variables included in this analysis were thyroid-stimulating hormone, total thyroxine (TT4), free triiodothyronine (FT3), total triiodothyronine (TT3), free thyroxine (FT4), antithyroglobulin, thyroglobulin, and antithyroid peroxidase levels. Generalized linear regression models were employed when estimating associations between MCV quartiles and thyroid parameters in 8104 adults 18 + years of age. In these participants, the weighted mean (SD) MCV was 89.36 (0.16) fL, with thyroid-stimulating hormone levels of 1.86 (0.03) mIU/mL, FT3 levels of 3.20 (0.01) pg/mL, FT4 levels of 0.80 (0.01) ng/dL, TT3 levels of 115.09 (0.64) ng/dL, and TT4 levels of 7.81 (0.04) µg/dL. When analyses were not adjusted, higher MCV values were related to reduced serum levels of FT3, TT3, or TT4. Following adjustment for possible confounding variables, this significant negative correlation between MCV and levels of FT3, TT3, and TT4 remained, and subgroup analysis revealed that this negative correlation was present in the male group and in the age group >50 years, but not in the female group and in the age group less than or equal to 50 years. These results suggest a significant negative correlation between MCV and FT3, TT3, and TT4, and this negative correlation originated more from the male population and those older than 50 years of age. The underlying mechanisms warrant additional investigation.

High-strength, antifogging and antibacterial ZnO/carboxymethyl starch/chitosan film with unique "Steel Wire Mesh" structure for strawberry preservation.

In this work, a multifunctional preservative film of ZnO/carboxymethyl starch/chitosan (ZnO/CMS/CS) with the unique "Steel Wire Mesh" structure is fabricated by the chemical crosslinked of ZnO NPs, CMS and CS. Unlike traditional nano-filled polymer film, the formation of the "Steel Wire Mesh" structure of ZnO/CMS/CS film is based on the synergistic effect of ZnO NPs filled CMS/CS and the coordination crosslinked between CMS/CS and Zn2+ derived from ZnO NPs. Thanks to the "Steel Wire Mesh" structure, the tensile strength and water vapor barrier of 2.5ZnO/10CMS/CS film are 2.47 and 1.73 times than that of CS film, respectively. Furthermore, the transmittance of 2.5ZnO/10CMS/CS film during antifogging test is close to 89 %, confirming its excellent antifogging effects. And the 2.5ZnO/10CMS/CS film also exhibits excellent long-acting antibacterial activity (up to 202 h), so it can maintain the freshness and appearance of strawberries at least 5 days. More importantly, the 2.5ZnO/10CMS/CS film is sensitive to humidity changes, which achieves real-time humidity monitoring of the fruit storage environment. Note that the preparation method of the film is safe, simple and environmentally friendly, and its excellent degradation performance will not bring any problems of food safety and environmental pollution.

Gadolinium Oxide Nanoparticles Reinforce the Fractionated Radiotherapy-Induced Immune Response in Tri-Negative Breast Cancer via cGAS-STING Pathway.

Introduction: Radiotherapy is a widely recognized first-line clinical treatment for cancer, but its efficacy may be impeded by the radioresistance of advanced tumors. It is urgent to improve the sensitivity of radioresistant tumors to radiotherapy. In this work, gadolinium oxide nanocrystals (GONs) were utilized as radiosensitizers to enhance the killing effect and reinforce the immune activation of X-ray irradiation on 4T1 breast cancer cells in vitro and in vivo. Methods: 1.0 T small animal MR imaging (MRI) system was employed to trace GONs in vivo, while 225 kVp X-ray irradiation equipment was utilized for investigating the radiosensitization of GONs in 4T1 breast cancer cells in vitro and in vivo. Western blot, quantitative real-time PCR (RT-qPCR), immunohistochemistry, immunofluorescence, clonal survival assay, flow cytometry and reactive oxygen species assay were used to explore the biological mechanism of GON sensitization. Results: GONs exhibited exceptional utility as contrast agents for both in vivo and in vitro MRI imaging. Interestingly, a single dose of 8.0 Gy X-rays together with GONs failed to confer superior therapeutic effects in tumor-bearing mice, while only 3.0 Gy × 3 fractions X-rays combined with GONs exhibited effective tumor growth inhibition. Moreover, fractionated X-ray irradiation with GONs demonstrated a superior capacity to activate the cGAS-STING pathway. Discussion: Fractionated X-ray irradiation in the presence of GONs has demonstrated the most significant activation of the anti-tumor immune response by boosting the cGAS-STING pathway.

The relationship between dietary inflammatory index values and thyroid function in the US adult population: An analysis of the NHANES 2007-2012 cohort.

OBJECTIVE: Researchers have developed the Dietary Inflammatory Index (DII) as a tool to quantify the inflammatory potential of a given diet. Higher DII scores indicated a more proinflammatory diet. While inflammation is known to have a strong impact on thyroid function, the precise nature of the association between DII scores and thyroid function has yet to be clarified. This study was conducted with the goal of exploring this relationship in a representative population of adults from the United States. METHODS: For this study, we used data from the National Health and Nutrition Examination Survey (NHANES). Standardized questionnaires were used to collect demographic and dietary data from the participants, and laboratory tests were used to collect data on the participants' thyroid parameters and other relevant data. Linear regression models and smoothed curve fitting were used to assess the relationship between DII scores and thyroid function, with weighted data analyses and subgroup analyses being conducted as appropriate. RESULTS: In total, 7712 subjects were recruited from the NHANES 2007-2012 cohort. Their weighted mean age was 44.87 (0.47) years, mean DII score was 1.41 (0.05). Mean FT3 was 3.20 (0.01) pg/mL and mean TT4 was 7.81 (0.03) µg/dL. In adjusted analyses, higher DII values were related to increases in FT3 (ß = .007; p = .027) and TT4 (ß = .050; p = .005) levels. Subgroup analyses showed a negative correlation between FT3 levels and DII scores in a population with high urinary iodine concentrations. CONCLUSION: These data indicate that the consumption of a more proinflammatory diet, as evidenced by elevated DII scores, is correlated with significant increases in FT3 and TT4 levels. However, for people with high urinary iodine concentrations, a more proinflammatory diet was associated with lower FT3 levels. Additional research will be vital to clarify the mechanistic basis for these findings.

The relationship between sleep duration and thyroid function in the adult US population: NHANES 2007-2012.

OBJECTIVE: Sleep disturbance is a common problem in the general population. Sleep deprivation or dysfunction can have profound health consequences. However, how sleep duration is associated with thyroid function remains unclear. This study was thus developed to examine the association between sleep duration and thyroid function in the US adult population. METHODS: A total of 8102 participants from the NHANES 2007-2012 dataset were included in this study. Weighted data analyses were conducted, and the link between sleep duration and thyroid function was probed using linear regression models with smoothed curve fitting. Stratified analyses were also performed. RESULTS: Weighted mean (standard deviation) values for study variables were as follows: sleep duration 6.85 (0.02) hours, thyroid-stimulating hormone (TSH) 1.86 (0.03) mIU/ml, serum free T3 3.20 (0. 01) pg/mL, serum free T4 0.80 (0.01) ng/dL, serum total T3 115.12 (0.64) ng/dL, serum total T4 7.81 (0.04) ug/dL, TPOAb 16.20 (1.53) IU/mL, TgAb 5.75 (0.73) IU/mL, and Tg 15.11 (0.46) ng/mL. In unadjusted analyses, increased sleep duration was associated with higher serum TSH levels and decreased FT3 levels. After adjustment for potential confounders, a significant negative relationship was detected between sleep duration and FT3 levels in participants with ≤7 hours of sleep. When sleep duration exceeded 7 hours, no significant changes in FT3 levels were observed after further increases in sleep duration. CONCLUSION: Increased sleep duration was related to decreased FT3 levels, primarily at short sleep durations, and this correlation was no longer evident when participants reached the recommended healthy sleep duration.

Ferroptosis: a novel regulated cell death participating in cellular stress response, radiotherapy, and immunotherapy.

BACKGROUND: Ferroptosis is a regulated cell death mode triggered by iron-dependent toxic membrane lipid peroxidation. As a novel cell death modality that is morphologically and mechanistically different from other forms of cell death, such as apoptosis and necrosis, ferroptosis has attracted extensive attention due to its association with various diseases. Evidence on ferroptosis as a potential therapeutic strategy has accumulated with the rapid growth of research on targeting ferroptosis for tumor suppression in recent years. METHODS: We summarize the currently known characteristics and major regulatory mechanisms of ferroptosis and present the role of ferroptosis in cellular stress responses, including ER stress and autophagy. Furthermore, we elucidate the potential applications of ferroptosis in radiotherapy and immunotherapy, which will be beneficial in exploring new strategies for clinical tumor treatment. RESULT AND CONCLUSION: Based on specific biomarkers and precise patient-specific assessment, targeting ferroptosis has great potential to be translated into practical new approaches for clinical cancer therapy, significantly contributing to the prevention, diagnosis, prognosis, and treatment of cancer.

Efficient Adsorption-Photocatalytic Removal of Tetracycline Hydrochloride over Octahedral MnS.

To disclose the effect of crystal plane on the adsorption-photocatalytic activity of MnS, octahedral MnS was prepared via the hydrothermal route to enhance the adsorption and photocatalytic efficiencies of tetracycline hydrochloride (TCH) in visible light region. The optimal MnS treated at 433 K for 16 h could remove 94.83% TCH solution of 260 mg L-1 within 180 min, and its adsorption-photocatalytic efficiency declined to 89.68% after five cycles. Its excellent adsorption-photocatalytic activity and durability were ascribed to the sufficient vacant sites of octahedral structure for TCH adsorption and the feasible band-gap structure for visible-light response. In addition, the band gap structure (1.37 eV) of MnS with a conduction band value of -0.58 eV and a valence band value of 0.79 eV was favorable for the generation of O2-, while unsuitable for the formation of OH. Hence, octahedral MnS was a potential material for the removal of antibiotics from wastewater.

Introducing a Novel Chemotherapeutic Drug for the Treatment of Lung Adenocarcinoma: Silver Nanoparticles Green-formulated by Cinnamomum verum.

In this study we report the green synthesis of nontoxic, stable, and small size silver nanoparticle by Cinnamomum verum with reducing/capping ability without any toxic reducing agents. The in situ prepared AgNPs were characterized by advanced physicochemical techniques like FE-SEM, TEM, and UV-Vis study. It has been established that AgNPs have a spherical shape with a mean diameter from 10 to 45 nm. In the antioxidant test, the IC50 of AgNPs and BHT against DPPH free radicals were 191 and 242 µg/mL, respectively. In the cellular and molecular part of the recent study, the treated cells with AgNPs were assessed by MTT assay for 48 h about the cytotoxicity and anti-human lung adenocarcinoma properties on normal (HUVEC) and lung adenocarcinoma cell lines i.e. PC-14, LC-2/ad, and HLC-1. The IC50 of AgNPs were 259, 291, and 395 µg/mL against PC-14, LC-2/ad, and HLC-1 cell lines, respectively. The viability of malignant lung cell line reduced dose-dependently in the presence of AgNPs.

PERK Regulates the Sensitivity of Hepatocellular Carcinoma Cells to High-LET Carbon Ions via either Apoptosis or Ferroptosis.

PERK is one of the transmembrane sensors of unfolded protein response (UPR) triggered by ER stress. In this study, we evaluated the role of PERK in the sensitivity of hepatocellular carcinoma (HCC) cells to high linear energy transfer (LET) carbon ions (CI). We found that CI irradiation could induce ER stress in HCC cells. On the one hand, PERK promoted autophagy via regulating ATF4 expression; on the other hand, PERK regulated p53 expression, and the latter either induced autophagy through up-regulating DRAM, or directly promoting apoptosis through the mitochondrial pathway or facilitating ferroptosis via down-regulating SLC7A11 (the extrinsic pathway), but independent of GPX4 (the intrinsic pathway). These factors jointly determined the sensitivity of HCC cells to high-LET CI radiation. Inhibiting TP53 directly increased cellular radioresistance definitely. Moreover, the death of HepG2 (TP53 wild type) cells induced by high-LET CI irradiation combined with sorafenib treatment might be caused by a mixed-type regulated cell death (RCD) including both apoptosis and ferroptosis, suggesting that apoptosis and ferroptosis are synergetic cell death modes regulated by TP53, which is one of the reasons why the sensitivity of HepG2 cells is higher than that of Hep3B (TP53 null type) and PLC/PRF5 (TP53 mutated type) cells. Therefore, our work might shed light on the potential therapeutic implication of CI radiotherapy combined with PERK targeted clinical drugs to implement personalized and precise treatment of HCCs.

Carbon Ion Radiotherapy Acts as the Optimal Treatment Strategy for Unresectable Liver Cancer During the Coronavirus Disease 2019 Crisis.

The coronavirus disease 2019 (COVID-19) pandemic has greatly disrupted the normal treatment of patients with liver cancer and increased their risk of death. The weight of therapeutic safety was significantly amplified for decision-making to minimize the risk of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Herein, the safety and effectiveness of carbon ion radiotherapy (CIRT) for unresectable liver cancer (ULC) were evaluated, and Chinese experiences were shared to solve the predicament of ULC treatment caused by SARS-CoV-2. Worldwide studies were collected to evaluate CIRT for ULC as the world has become a community due to the COVID-19 pandemic. We not only searched five international databases including the Cochrane Library, Web of Science, PubMed, Embase, and Scopus but also performed supplementary retrieval with other sources. Chinese experiences of fighting against COVID-19 were introduced based on the advancements of CIRT in China and a prospective clinical trial of CIRT for treating ULC. A total of 19 studies involving 813 patients with ULC were included in the systematic review. The qualitative synthetic evaluation showed that compared with transarterial chemoembolization (TACE), CIRT could achieve superior overall survival, local control, and relative hepatic protection. The systematic results indicated that non-invasive CIRT could significantly minimize harms to patients with ULC and concurrently obtain superior anti-cancer effectiveness. According to the Chinese experience, CIRT allows telemedicine within the hospital (TMIH) to keep a sufficient person-to-person physical distance in the whole process of treatment for ULC, which is significant for cutting off the transmission route of SARS-CoV-2. Additionally, CIRT could maximize the utilization rate of hospitalization and outpatient care (UHO). Collectively, CIRT for ULC patients not only allows TMIH and the maximized UHO but also has the compatible advantages of safety and effectiveness. Therefore, CIRT should be identified as the optimal strategy for treating appropriate ULC when we need to minimize the risk of SARS-CoV-2 infection and to improve the capacity of medical service in the context of the unprecedented COVID-19 crisis.

The Relationship between Time to Surgery (TTS) and Survival in Breast Cancer: A Systematic Review and Meta-Analysis.

BACKGROUND: Curative operation is the practical and primary therapy for masses of breast cancers. In contrast, the correlation between the time interval from breast cancer diagnosis to curative surgery and survival is still uncertain. METHODS: An electronic literature search was conducted on PubMed/Medline and EMBASE (between Jan 2000 and Jan 2020). Primary endpoints were overall survival (OS) or Disease-Free Survival (DFS). The HR with 95% confidence intervals were calculated using a random-effects or fixed-effects model. RESULTS: The combined HR for OS was 1. 10 (95% CI 1. 08-1. 11; P=0. 000) by fixed-effects model, no statistically significant heterogeneity was found (P=1. 000; I2=0%), and this difference was statistically significant (Z=11. 99; P=0. 000). CONCLUSION: This meta-analysis showed a significant adverse association between more prolonged time to surgery (TTS) and lower overall survival in patients with breast cancer. It is reasonable to minimize that interval between diagnosis and curative surgery.

Hyperthermia ablation combined with transarterial chemoembolization versus monotherapy for hepatocellular carcinoma: A systematic review and meta-analysis.

BACKGROUND AND AIMS: The existing evidence has indicated that hyperthermia ablation (HA) and HA combined with transarterial chemoembolization (HATACE) are the optimal alternative to surgical resection for patients with hepatocellular carcinoma (HCC) in the COVID-19 crisis. However, the evidence for decision-making is lacking in terms of comparison between HA and HATACE. Herein, a comprehensive evaluation was performed to compare the efficacy and safety of HATACE with monotherapy. MATERIALS AND METHODS: Worldwide studies were collected to evaluate the HATACE regimen for HCC due to the practical need for global extrapolation of applicative population. Meta-analyses were performed using the RevMan 5.3 software (The Nordic Cochrane Centre, The Cochrane Collaboration, Copenhagen, Denmark). RESULTS: Thirty-six studies involving a large sample of 5036 patients were included finally. Compared with HA alone, HATACE produced the advantage of 5-year overall survival (OS) rate (OR:1.90; 95%CI:1.46,2.46; p < 0.05) without increasing toxicity (p ≥ 0.05). Compared with TACE alone, HATACE was associated with superior 5-year OS rate (OR:3.54; 95%CI:1.96,6.37; p < 0.05) and significantly reduced the incidences of severe liver damage (OR:0.32; 95%CI:0.11,0.96; p < 0.05) and ascites (OR:0.42; 95%CI:0.20,0.88; p < 0.05). Subgroup analysis results of small (≤3 cm) HCC revealed that there were no significant differences between the HATACE group and HA monotherapy group in regard to the OS rates (p ≥ 0.05). CONCLUSIONS: Compared with TACE alone, HATACE was more effective and safe for HCC. Compared with HA alone, HATACE was more effective for non-small-sized (>3 cm) HCC with comparable safety. However, the survival benefit of adjuvant TACE in HATACE regimen was not found for the patients with small (≤3 cm) HCC.

Comparable radiation sensitivity in p53 wild-type and p53 deficient tumor cells associated with different cell death modalities.

Studies of radiation interaction with tumor cells often take apoptosis as the desired results. However, mitotic catastrophe and senescence are also promoted by clinically relevant doses of radiation. Furthermore, p53 is a well-known transcription factor that is closely associated with radiosensitivity and radiation-induced cell death. Therefore, we aimed to investigate the involvement of radiosensitivity, cell death modalities and p53 status in response to carbon-ion radiation (CIR) here. Isogenic human colorectal cancer cell lines HCT116 (p53+/+ and p53-/-) were irradiated with high-LET carbon ions. Cell survival was determined by the standard colony-forming assay. 53BP1 foci were visualized to identify the repair kinetics of DNA double-strand breaks (DSBs). Cellular senescence was measured by SA-ß-Gal and Ki67 staining. Mitotic catastrophe was determined with DAPI staining. Comparable radiosensitivities of p53+/+ and p53-/- HCT116 colorectal cells induced by CIR were demonstrated, as well as persistent 53BP1 foci indicated DNA repair deficiency in both cell lines. Different degree of premature senescence in isogenic HCT116 colorectal cancer cells suggested that CIR-induced premature senescence was more dependent on p21 but not p53. Sustained upregulation of p21 played multifunctional roles in senescence enhancement and apoptosis inhibition in p53+/+ cells. p21 inhibition further increased radiosensitivity of p53+/+ cells. Complex cell death modalities rather than single cell death were induced in both p53+/+ and p53-/- cells after 5 Gy CIR. Mitotic catastrophe was predominant in p53-/- cells due to inefficient activation of Chk1 and Chk2 phosphorylation in combination with p53 null. Senescence was the major cell death mechanism in p53+/+ cells via p21-dependent pathway. Taken together, p21-mediated premature senescence might be used by tumor cells to escape from CIR-induced cytotoxicity, at least for a time.

Therapeutic Efficacy of Carbon Ion Irradiation Enhanced by 11-MUA-Capped Gold Nanoparticles: An in vitro and in vivo Study.

PURPOSE: Gold nanoparticles (AuNPs) are widely studied as radiosensitizers, but their radiosensitization in carbon ion radiotherapy is unsatisfactory. There is a lack of in vivo data on the radiosensitization of AuNPs under carbon ion irradiation. This study focused on the radiosensitization effect of AuNPs in the mouse melanoma cell line B16-F10 in vitro and in vivo. MATERIALS AND METHODS: 11-mercaptoundecanoic acid (11-MUA)-coated gold (Au) nanoparticles (mAuNPs) formulations were prepared and characterized. To verify the radiosensitization effect of mAuNPs, hydroxyl radicals were generated in aqueous solution, and the detection of intracellular reactive oxygen species (ROS) and clone survival were carried out in vitro. The tumor growth rate (TGR) and survival of mice were analyzed to verify the radiosensitization effect of mAuNPs in vivo. The apoptosis of tumor cells was detected, and the expression of key proteins in the apoptosis pathway was verified by immunohistochemistry. RESULTS: The intracellular ROS level in B16-F10 cells was enhanced by mAuNPs under carbon ion irradiation. The sensitization rate of mAuNPs was 1.22 with a 10% cell survival rate. Compared with irradiation alone, the inhibitory effect of mAuNPs combined with carbon ion irradiation on tumor growth was 1.94-fold higher, the survival time of mice was prolonged by 1.75-fold, and the number of apoptotic cells was increased by 1.43-fold. The ratio of key proteins Bax and Bcl2 in the apoptosis pathway was up-regulated, and the expression of caspase-3, a key executor of the apoptosis pathway, was up-regulated. CONCLUSION: In in vivo and in vitro experiments, mAuNPs showed radiosensitivity to carbon ion irradiation. The sensitization effect of mAuNPs on mice tumor may be achieved by activating the mitochondrial apoptosis pathway and increasing tumor tissue apoptosis. To our best knowledge, the present study is the first in vivo evidence for radiosensitization of mAuNPs in tumor-bearing mice exposed to carbon ion irradiation.

Efficient adsorption of ciprofloxacin using Ga2S3/S-modified biochar via the high-temperature sulfurization.

Ga2S3 and sulfur co-modified biochar (Ga/S-BC) composites were prepared for enhancing the adsorption of ciprofloxacin from sugarcane bagasse via the high-temperature sulfurization. In contrast with sulfur-modified biochar, Ga/S-BC exhibited the better adsorption capacity for ciprofloxacin removal. The increasing Ga content induced to the climbing and then declining adsorption activity of Ga/S-BC. Among these obtained Ga/S-BC composites, optimal 3-Ga/S-BC with a Ga content of 7.40% and surface area of 681.67 m2 g-1 exhibited the superior capacity of 330.21 mg g-1. The adsorption capacity of 3-Ga/S-BC declined to 301.66 mg g-1 after nine cycles. pH and inorganic salts also affected the adsorption capacity of 3-Ga/S-BC for ciprofloxacin removal. The adsorption isotherms of obtained Ga/S-BC composites were well described by Langmuir isotherm, and their adsorption kinetics were well estimated via second-order model. The adsorption performance of 3-Ga/S-BC in ciprofloxacin removal was a physisorption and spontaneous process.

Flower-like Bi2S3-In2S3 heterojunction for efficient solar light induced photoreduction of Cr(VI).

To develop Bi2S3-based heterojunction for efficient solar light induced photoreduction of Cr(VI), flower-like Bi2S3-In2S3 composites consisted of nanorods were prepared via a microwave-assisted hydrothermal route. In contrast with pure Bi2S3, Bi2S3-In2S3 composites exhibited the enhanced photoreduction activity while the decreased adsorption capacity for Cr(VI) removal. The best removal efficiency of 70 mg L-1 Cr(VI) solution (99.86%) was achieved by the optimal 3-Bi2S3-In2S3 with a Bi/In molar ratio of 4:1 within 140 min. It's ascribed to the narrow band gap for strengthened visible-light response, the tight interface between Bi2S3 and In2S3 for rapid transfer and separation of charge carriers, and the enough S vacancies for highly-efficient active sites of adsorption-photoreduction. However, the long-term photo-corrosion resulted in the slightly inferior reusability of 3-Bi2S3-In2S3 under solar light irradiation after five cycles.

Genistein inhibits radiation-induced invasion and migration of glioblastoma cells by blocking the DNA-PKcs/Akt2/Rac1 signaling pathway.

BACKGROUND AND PURPOSE: Radiotherapy is the most important therapeutic measure against glioblastoma multiforme (GBM), which is regarded as the most common and highly lethal type of brain cancer. Nevertheless, most relapses originate in the close vicinity of the irradiated target volume. Genistein is a natural product that can suppress the invasive potential of cancer cells. In this study, DNA-dependent protein kinase catalytic subunit (DNA-PKcs)-proficient and -deficient GBM cells were selected for in vitro and in vivo studies to investigate the inhibiting effects of genistein on radiation-induced invasion and migration and the corresponding mechanism. MATERIALS AND METHODS: GBM cell lines with or without genistein pre-treatment were irradiated with X-rays. Cell survival was determined using colony formation assay and the rate of cellular proliferation was analyzed with a real-time cell electronic sensing system. For in vitro study, invasion and migration abilities were evaluated via wound-healing and transwell assays, while protein expression was determined with western blotting. Genistein interaction with DNA-PKcs was estimated with pull-down, recombinant and binding assays. For in vivo study, cells were stereotactically injected into NOD-SCID mice to establish tumors. Hematoxylin and eosin and immunohistochemistry were used to assess the invasive potential of GBM. RESULTS: X-ray irradiation enhanced the migration and invasion of DNA-PKcs-positive but not DNA-PKcs-negative GBM cells. It also activated the DNA-PKcs/Akt2/Rac1 signaling pathway, which contributed to GBM malignant progression by aggravating GBM cell invasive potential. The study successfully demonstrated that genistein can specifically bind to DNA-PKcs and block the DNA-PKcs/Akt2/Rac1 pathway, thereby effectively inhibiting radiation-induced invasion and migration of GBM cells in vitro and in vivo. The present study emphasized that radiation-induced invasive potential is initiated by DNA-PKcs, which is a well-known double strand breaks (DSB) repair protein, and determined the exact site for genistein binding to DNA-PKcs. CONCLUSION: DNA-PKcs is not only a potential target for cancer therapy, but also a reliable biomarker for predicting radiation-induced invasion and migration of GBM cells. Thus, genistein might serve as a novel therapeutic strategy for treating GBM.