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Hyperlipidemia, characterized by an abnormal lipid metabolism, is related to multiple cardiovascular diseases that pose challenges to global public health. Macadamia oil (MO), rich in monounsaturated fatty acids (around 80%), is regarded as a functional oil used to regulate lipid accumulation. Nonetheless, the lipid-lowering mechanism of MO is still unknown. Therefore, the lipid-lowering effects of MO in high-fat diet (HFD)-induced hyperlipidemic mice were evaluated in this study. The results revealed that MO could effectively reduce body weight and the organ index and improve serum lipid levels by reducing total cholesterol, triglycerides, and low-density lipoprotein cholesterol levels and elevating high-density lipoprotein cholesterol levels. Additionally, MO supplementation could improve abnormal liver function caused by hyperlipemia, characterized by decreased liver enzyme levels, including alanine aminotransferase and aspartate aminotransferase. Meanwhile, MO also exhibited an inhibitory effect on oxidative stress and lipid accumulation caused by an HFD. Moreover, findings from qRT-PCR and Western blotting analyses suggest that MO supplementation markedly prevented hyperlipidemia by inhibiting the expression of AMPK pathway-related genes, SREBP-1c, FAS, ACC, and PPAR-γ, as well as upregulating the levels of Nrf2, HO-1, and γ-GCS. These results indicate that MO attenuates lipid accumulation in vivo via AMPK/Nrf2 pathway activation, suggesting that MO could serve as a dietary supplementation or medication for treating hyperlipidemia.

Abstract Ionizing radiation (IR) causes a wide variety of DNA lesions, of which DNA double-stranded breaks (DSBs) are the most deleterious. Homologous recombination (HR) is a crucial route responsible for repairing DSBs. RecQ-mediated genome instability protein 1 (RMI1) is a member of an evolutionarily conserved Bloom syndrome complex, which prevents and resolves aberrant recombination products during HR, thereby promoting genome stability. However, little is known about the role of RMI1 in regulating the cellular response to IR. This study aimed to understand the cellular functions and molecular mechanisms by which RMI1 maintains genomic stability after IR exposure. Here, we showed IR upregulated the RMI1 protein level and induced RMI1 relocation to the DNA damage sites. We also demonstrated that the loss of RMI1 in cells resulted in enhanced levels of DNA damage, sustained cell cycle arrest, and impaired HR repair after IR, leading to reduced cell viability and elevated genome instability. Taken together, our results highlighted the direct roles of RMI1 in response to DNA damage induced by IR and implied that RMI1 might be a new genome safeguard molecule to radiation-induced damage.

Abstract Background Dysregulation of gut microbiota–host bile acid (BA) co-metabolism is a critical pathogenic factor of diarrhea-predominant irritable bowel syndrome (IBS-D). Traditional Chinese Medicine (TCM), instructed by pattern differentiation, is effective in treating IBS-D, in which liver depression and spleen deficiency (LDSD) is the most prevalent pattern. Still, it is unclear the linkage between the LDSD pattern and the BA metabolic phenotype. Purpose This study aimed to uncover the biological basis of the LDSD pattern from the BA metabolic perspective. Methods Patients with IBS-D completed questionnaires regarding the irritable bowel severity scoring system (IBS-SSS), stool frequency, Stool Bristol scale, and Self-Rating Scales of mental health. Fasting blood and morning feces were collected to analyze the gut metagenome and BA-related indices/metabolites. Results IBS-D patients with LDSD had a higher incidence of BA overexcretion (41% vs. 23% non-LDSD) with significant elevations in fecal total BAs and serum BA precursor 7α-hydroxy-4-cholesten-3-one levels. Compared to controls or non-LDSD patients, LDSD patients had a featured fecal BA profile, with higher proportions of deoxycholic acid (DCA), 7-ketodeoxycholic acid, and lithocholic acid. It is consistent with the BA-metabolizing genomic changes in the LDSD gut microbiota characterized by overabundances of 7-dehydroxylating bacteria and BA-inducible genes (baiCD/E/H). The score of bowel symptoms (stool frequency and abdominal pain) showing greater severity in the LDSD pattern were positively correlated with bai-expressing bacterial abundances and fecal DCA levels separately. Conclusion We clarified a differed BA metabolic phenotype in IBS patients with LDSD, which closely correlates with the severity of bowel symptoms. It demonstrates that gut microbiota and host co-metabolism of BAs would provide crucial insight into the biology of the LDSD pattern and its internal relationship with IBS progression.

Abstract Background The transmembrane receptor Kremen2 has been reported to participate in the tumorigenesis and metastasis of gastric cancer. However, the role of Kremen2 in non-small cell lung cancer (NSCLC) and the underlying mechanism remain unclear. This study aimed to explore the biological function and regulatory mechanism of Kremen2 in NSCLC. Methods The correlation between Kremen2 expression and NSCLC was assessed by analyzing the public database and clinical tissue samples. Colony formation and EdU assays were performed to examine cell proliferation. Transwell and wound healing assays were used to observe cell migration ability. Tumor-bearing nude mice and metastatic tumor models were used to detect the in vivo tumorigenic and metastatic abilities of the NSCLC cells. An immunohistochemical assay was used to detect the expression of proliferation-related proteins in tissues. Western blot, immunoprecipitation and immunofluorescence were conducted to elucidate the Kremen2 regulatory mechanisms in NSCLC. Results Kremen2 was highly expressed in tumor tissues from NSCLC patients and was positively correlated with a poor patient prognosis. Knockout or knockdown of Kremen2 inhibited cell proliferation and migration ability of NSCLC cells. In vivo knockdown of Kremen2 inhibited the tumorigenicity and number of metastatic nodules of NSCLC cells in nude mice. Mechanistically, Kremen2 interacted with suppressor of cytokine signaling 3 (SOCS3) to maintain the epidermal growth factor receptor (EGFR) protein levels by preventing SOCS3-mediated ubiquitination and degradation of EGFR, which, in turn, promoted activation of the PI3K-AKT and JAK2-STAT3 signaling pathways. Conclusions Our study identified Kremen2 as a candidate oncogene in NSCLC and may provide a potential target for NSCLC treatment.

Background: Colorectal cancer (CRC) is the third most common malignancy and the second deadliest cancer worldwide. Metastasis to the liver, the most common metastatic site in CRC, is the leading cause of death in patients with CRC. Hyperlipidemia, which is common in patients with CRC, promotes CRC progression and metastasis. Hyperlipidemia is commonly observed in obese patients and is often induced by hypernutrition. The underlying mechanism of hypernutrition-induced hyperlipidemia in promoting CRC liver metastasis remains unclear, and there is an unmet need for effective and low-cost treatments for patients with CRC. Methods: A mouse cecum orthotopic CRC model combined with high-fat diet (HFD) feeding, was established to mimic liver metastasis in CRC in obese patients. The effects of Dachaihu decoction (DCHD), a traditional herbal medicine used to treat inflammation and nonalcoholic fatty liver disease, and of the conventional prescription medicine obeticholic acid (OCA) were evaluated. HFD-induced obesity, hyperlipidemia, and CRC liver metastasis were assessed, along with the histology and pathology of the liver and intestine and the expression of metabolic genes in these tissues. The effects of DCHD and OCA on HFD-induced outcomes were evaluated, and human umbilical vein endothelial cells (HUVECs) treated with bile acids (BAs) and DCHD were used to study the underlying mechanisms in vitro. Results: HFD-mediated obesity and hyperlipidemia promoted CRC metastasis, accompanied by disruption of the gut vascular barrier (GVB) and altered bile acid (BA) metabolism. DCHD decreased HFD-induced hyperlipidemia and liver metastasis in CRC, improving overall survival. Those effects of DCHD were equivalent to or better than those of OCA. DCHD regulated the expression of genes of BA metabolism and tight junctions (TJ) to prevent HFD-induced disruption of the GVB. In HUVECs, DCHD prevented the increases in intracellular Ca2+ and accumulation of reactive oxygen species induced by primary conjugated BAs, assisting in the maintenance of redox homeostasis and preventing the downregulation of TJ proteins, thereby maintaining the integrity of the endothelial barrier. Conclusions: The data provide a link between hypernutrition and GVB disruption, which contributes to high liver metastasis in patients with CRC. DCHD may represent a novel therapy in CRC, and targeting abnormal lipid metabolism could be a promising therapeutic strategy for avoiding hypernutrition-associated CRC metastasis.

Abstract In the frame of radiotherapy treatment of cancer, radioresistance remains a major issue that still needs solutions to be overcome. To effectively improve the radiosensitivity of tumors and reduce the damage of radiation to neighboring normal tissues, radiosensitizers have been given increasing attention in recent years. As nanoparticles based on the metal element gadolinium, AGuIX nanoparticles have been shown to increase the radiosensitivity of cancers. Although it is a rare nanomaterial that has entered preclinical trials, the unclear biological mechanism hinders its further clinical application. In this study, we demonstrated the effectiveness of AGuIX nanoparticles in the radiosensitization of triple-negative breast cancer. We found that AGuIX nanoparticles increased the level of DNA damage by compromising the homologous recombination repair pathway instead of the non-homologous end joining pathway. Moreover, the results showed that AGuIX nanoparticles induced apoptosis, but the degree of apoptosis ability was very low, which cannot fully explain their strong radiosensitizing effect. Ferroptosis, the other mode of cell death, was also discovered to play a significant role in radiation sensitization, and AGuIX nanoparticles may regulate the anti-ferroptosis system by inhibiting the NRF2-GSH-GPX4 signaling pathway. Graphical Abstract

Objective: We aimed to investigate the radiosensitizing efficacy of the poly-ADP-ribose polymerase (PARP) inhibitor, olaparib, and the Bloom syndrome protein (BLM) helicase inhibitor, ML216, in non-small cell lung cancer (NSCLC) cells. Methods: Radiosensitization of NSCLC cells was assessed by colony formation and tumor growth assays. Mechanistically, the effects of ML216, olaparib, and radiation on cell and tumor proliferation, DNA damage, cell cycle, apoptosis, homologous recombination (HR) repair, and non-homologous end joining (NHEJ) repair activity were determined. Results: Both olaparib and ML216 enhanced the radiosensitivities of olaparib-sensitive H460 and H1299 cells, which was seen as decreased surviving fractions and Rad51 foci, increased total DNA damage, and γH2AX and 53BP1 foci (P < 0.05). The expressions of HR repair proteins were remarkably decreased in olaparib-treated H460 and H1299 cells after irradiation (P < 0.05), while olaparib combined with ML216 exerted a synergistic radiosensitization effect on olaparib-resistant A549 cells. In addition to increases of double strand break (DSB) damage and decreases of Rad51 foci, olaparib combined with ML216 also increased pDNA-PKcs (S2056) foci, abrogated G2 cell cycle arrest, and induced apoptosis in A549 lung cancer after irradiation in vitro and in vivo (P < 0.05). Moreover, Western blot showed that olaparib combined with ML216 and irradiation inhibited HR repair, promoted NHEJ repair, and inactivated cell cycle checkpoint signals both in vitro and in vivo (P < 0.05). Conclusions: Taken together, these results showed the efficacy of PARP and BLM helicase inhibitors for radiosensitizing NSCLC cells, and supported the model that BLM inhibition sensitizes cells to PARP inhibitor-mediated radiosensitization, as well as providing the basis for the potential clinical development of this combination for tumors intrinsically resistant to PARP inhibitors and radiotherapy.

Objective: The aim of the present study was to investigate the mechanisms responsible for the radiation-sensitizing effect of antennapedia proteins, ANTP-SMACN7, on lung cancer cells treated with accelerated carbon and Fe particle irradiation. Methods: The ANTP-SMACN7 fusion peptide was synthesized and linked to fluorescein isothiocyanate to determine its ability to penetrate cells. A549 and NCI-H460 cells, human non-small cell lung cancer (NSCLC) cell lines, were irradiated with X-ray or high linear energy transfer (LET) irradiation with or without ANTP-SMACN7 treatment. Cellular survival, apoptosis, and protein expression were studied by colony formation assays, flow cytometry, and western blot analyses, respectively. Results: ANTP-SMACN7 fusion proteins entered the cells and promoted A549 and NCI-H460 cell high LET irradiation radiosensitization. High LET irradiation was more efficient for clonogenic cell killing and the induction of apoptosis (P < 0.05). Treatment with ANTP-SMACN7 significantly reduced the A549 and NCI-H460 cell clone-forming percentages and increased apoptosis through inhibition of the X-linked inhibitor of apoptosis protein and the activation of caspase-3 and caspase-9. Conclusions: Regarding pharmaceutical radiosensitization, these findings provided a way to improve high-LET clinical radiotherapy for NSCLC patients.

Background: It has been well-established that acute radiation exposures increase the risk of leukemia. However, it is still unknown whether these leukemia risk estimates could be extrapolated to occupational populations who receive repeated low-dose radiation exposure. The purpose of this study was to estimate quantified associations between low-dose radiation exposures and leukemia. Methods: The Chinese medical X-ray worker study (CMXW) included 27,011 medical X-ray workers employed at major hospitals in 24 provinces in China from 1950 to 1980, and a control population of 25,782 physicians matched by hospital, who were unexposed to X-ray equipment. Poisson regression models were used to estimate the excess relative risk (ERR) and excess absolute risk (EAR) for the incidence of leukemia associated with cumulative doses. A meta-analysis of the published literature on low-dose occupational radiation exposure and leukemia risk was also conducted. Results: The incidence rates of leukemia in X-ray workers and the control group were 6.70 and 3.39 per 100,000 person-years, respectively. Among X-ray workers, the average cumulative red bone marrow dose was 0.046 Gy. We found a positive relationship between 2-year lagged cumulative red bone marrow dose and risk of leukemia excluding chronic lymphocytic leukemia (CLL) (ERR = 0.66 per 100 mGy, 90% CI: 0.091.53; EAR = 0.29 per 104 PY-100 mGy, 90% CI: 0.070.56). The excess risk was largely driven by myeloid leukemia (ERR = 1.06 per 100 mGy, 90% CI: 0.22, 2.51). Based on the meta-analysis, the pooled ERR at 100 mGy was 0.19 (95% CI: 0.080.31). Conclusion: This study provides strong evidence of a positive and linear doseresponse relationship between cumulative red bone marrow dose and the incidence of non-CLL leukemia.

Nervonic acid plays an important role in nutrition and function of the human body. Malania oleifera, Acer truncatum and Xanthoceras sorbifolium are China’s unique woody plant rich in nervonic acid in seed oil. This study aims to investigate the lipid composition of these 3 special resources. Their fatty acids were detected by gas chromatography coupled with flame detector (GC-FID). Triglycerides (TAGs) and phospholipids (PLs) were detected by shotgun-mass spectrometry (shotgun-MS). Results showed that M. oleifera oil presented the highest level of nervonic acid (46.20 ​± ​0.22%) among the 3 oils. Seeds oil of A. truncatum and X. sorbifolium had 3.53 ​± ​0.20% and 1.83 ​± ​0.21% nervonic acid respectively. 53 species of TAGs and 15 species of PLs were identified in M. oleifera oil, with PLs content of 499.94 ​± ​22.34 ​μg/g. In A. truncatum oil, PL and TAG species were twice more than those in M. oleifera oil, and its’ content of PLs was 76.27 ​± ​3.21 ​μg/g. In X. sorbifolium oil, 75 TAGs and 34 ​PLs were detected, with the lowest PLs at 23.84 ​± ​0.17 ​μg/g. The results demonstrated that these 3 vegetable oils have great potential to become nervonic acid supplements for human health.

Red pitaya (Hylocereus undatus) is an essential tropical fruit in China. To make more rational use of its processing, byproducts and fruit seeds, and the type, composition, and relative content of lipids in pitaya seed oil were analyzed by UPLC-TOF-MS/MS. The results showed that the main fatty acids in pitaya seed oil were linoleic acid 42.78%, oleic acid 27.29%, and palmitic acid 16.66%. The ratio of saturated fatty acids to unsaturated fatty acids to polyunsaturated fatty acids was close to 1:1.32:1.75. The mass spectrum behavior and fracture mechanism of four lipid components, TG 54:5|TG 18:1_18:2_18:2, were analyzed. In addition, lipids are an essential indicator for evaluating the quality of oils and fats, and 152 lipids were isolated and identified from pitaya seed oil for the first time, including 136 glycerides and 16 phospholipids. The main components of glyceride and phospholipids were triglycerides and phosphatidyl ethanol, providing essential data support for pitaya seed processing and functional product development.

CTC1 is a component of the mammalian CST (CTC1–STN1–TEN1) complex which plays essential roles in resolving replication problems to facilitate telomeric DNA and genomic DNA replication. We previously reported that the depletion of CTC1 leads to stalled replication fork restart defects. Moreover, the mutation in CTC1 caused cancer-prone diseases including Coats plus (CP) or dyskeratosis congenita (DC). To better understand the CTC1 regulatory axis, the microRNAs (miRNAs) targeting to CTC1 were predicted by a bioinformatics tool, and the selected candidates were further confirmed by a dual-luciferase reporter assay. Here, our current results revealed that miR-376a significantly reduced CTC1 expression at the transcription level by recognizing CTC1 3′-UTR. In addition, the overexpression of miR-376a induced telomere replication defection and resulted in direct replicative telomere damage, which could be rescued by adding back CTC1. Telomere shortening was also observed upon miR-376a treatment. Furthermore, for the clinical patient samples, the high expression of miR-376a was associated with the deregulation of CTC1 and a poor outcome for the rectum adenocarcinoma patients. Together, our results uncovered a novel role of miR-376a in stimulating rectum adenocarcinoma progression via CTC1 downregulating induced telomere dysfunction.

With the extensive application of radiotherapy in various cancers, its side effects in tissues adjacent to cancers are garnering much attention. Intestines are sensitive to irradiation due to its rapid proliferation, and irradiation-induced enteric inflammation is common in patients with pelvic peritoneal tumors. Sirt1, class III protein deacetylase, could lead to transcriptional repression of various inflammation-associated genes, and our previous study has proved its relationship with interleukin (IL)-1β. Here we show that resveratrol, the activator of Sirt1, could alleviate the bowel inflammation induced by irradiation and the expression of Sirt1 is consistent with the inflammation level. We further identified in vivo that Sirt1 repress the expression of IL-1β by the repression of NLR Family, Pyrin Domain Containing protein 3 (NLRP3) expression. In conclusion, this study confirms resveratrol acts against radiation-induced inflammatory bowel disease via NLRP-3 inflammasome repression in mice and supports Sirt1 as a potential biomarker and therapy target in intestinal radiation protection.

Mesenchymal stem cells (MSCs) derived from different tissues may aid in the regeneration of radiation-induced organ lesions; however, the radiation responses of human MSCs from different sources are unknown. In our study, a comparison of the results from cell proliferation, apoptosis, cell cycle, DNA damage, and DNA repair assays consistently showed that MSCs derived from adipose tissue possess a significantly stronger radiation resistance capacity than MSCs derived from umbilical cord and gingival, which is accompanied by a higher level of phosphorylated signal transducer and activator of transcription 3 (Stat3) expression. This reminds us Stat3 could be a potential biomarker of radiation resistance. These findings provide a better understanding of radiation-induced biologic responses in MSCs and may lead to the development of better strategies for stem cell treatment and cancer therapy.

Abstract Background Cytokine-based cancer therapies have attracted a great deal of attention in recent years. Unfortunately, resistance to treatment limits the efficacy of these therapeutics. Therefore, the aim of our study was to explore the mechanism of IL-2-based therapy for hepatocellular carcinoma in an attempt to increase the efficiency of this treatment option. Methods HepG2 cells were treated with IL-2. Then, siRNA against TZA was used to transfected into HepG2 cells. Cellular apoptosis was measured via MTT assay, TUNEL assay and caspase-3 activity. Cellular proliferation was evaluated via EdU assay and western blotting. Cellular migration was detected via Transwell assay. Mitochondrial function was monitored by mitochondrial potential analysis, ROS staining, immunofluorescence and western blotting. Pathway blocker and activator were used to establish the role of JNK/F-actin/mitochondrial fission signaling pathway in HepG2 cells stress response. Results Our study found that IL-2 treatment significantly reduced the viability, mobility and proliferation of HepG2 cells in vitro. We also demonstrated that IL-2 treatment was accompanied by an increase in the expression of transcriptional co-activator with PDZ-binding motif (TAZ). Interestingly, genetic ablation of TAZ in the presence of IL-2 further promoted apoptosis, inhibited mobility, and arrested proliferation in HepG2 cells. At the molecular level, IL-2 administration activated excessive mitochondrial fission via the JNK/F-actin pathway; these effects were further enhanced by TAZ deletion. Mechanistically, TAZ knockdown further increased the expression of mitochondrial fission-related proteins such as Drp1, Mff and Fis. The augmented mitochondrial fission stimulated ROS overproduction, mediated redox imbalance, interrupted mitochondrial energy generation, reduced mitochondrial membrane potential, promoted leakage of the pro-apoptotic molecule cyt-c into the nucleus, and initiated caspase-9-related mitochondrial death. Further, we demonstrated that the anti-proliferative and anti-metastatic effects of IL-2 in HepG2 cells were enhanced by TAZ deletion, suggesting that IL-2 sensitizes HepG2 cells to IL-2-based cytokine therapy. However, JNK/F-actin pathway blockade could abrogate the inhibitory effects of TAZ deletion on HepG2 migration, proliferation and survival. Conclusions Taken together, our data indicate that the anti-tumor effects of IL-2-based therapies may be enhanced by TAZ deletion in a JNK/F-actin pathway-dependent manner. This finding provides a novel combinatorial therapeutic approach for treating hepatocellular carcinoma that might significantly increase the efficacy of cytokine-based therapies in a clinical setting.

Background: Managing and recycling electronic waste (e-waste), while useful and necessary, has resulted in significant contamination of several environments in China. The area around Tianjin, China has become one of the world's largest e-waste disposal centers, where electronics are processed by manually disassembly or burning, which can result in serious exposure of workers to a multitude of toxicants. Objective: The present study assessed potential genomic damage in workers involved in recycling e-waste. Methods: To detect cytogenetic and DNA damage, chromosomal aberrations (CA), cytokinesis blocking micronucleus (CBMN) and the comet assay were performed. Concentrations of some trace elements, markers of oxidative stress and polychlorinated biphenyls (PCBs) in whole blood or serum were measured, and relationships among the markers described above, age, and duration of exposure were analyzed. The profiles of expression of genes in lymphocytes in peripheral blood were assessed to determine the status of the regulation of genes involved in genome stability. Results: Concentrations of 28 PCB congeners in the whole blood of the exposed group were significantly (P

Background/Aims: SirT1, a conserved NAD+-dependent deacetylase, has been implicated in modulating cell survival and stress responses, and it appears to play an important role in tumorigenesis and cancer resistance to chemoradiotherapy. The mechanism of SirT1 in cancer chemoradiotherapy remains to be further elucidated, which could provide potential targets for cancer therapy. Methods: We performed colony formation, immunofluorescence microscopy, flow cytometry, RNA interference, and western blotting assays to determine whether SirT1 regulates radiation sensitization and which mechanisms and/or pathways it takes in lung cancer cell lines A549 and H460. Results: Initially, the expression of SirT1 was found to be negatively correlated with radiosensitivity in lung cancer cell lines A549 and H460. RNA interference with siSirT1 against SirT1 specifically reduced SirT1 expression and induced radiosensitivity both in A549 and H460 cell lines. In contrast, the radiosensitivity was significantly reduced once SirT1 was activated by resveratrol. Immunofluorescence assay and apoptosis analysis indicated that the effect of SirT1 on the radiosensitivity observed in the A549 and H460 cell lines was mainly achieved by regulating DNA damage repair and apoptosis processes. Furthermore, the expression of SirT1 negatively modulated the expression of apoptosis-related protein NF-κB and its downstream regulator of Smac. Conclusion: Our results indicate that SirT1 regulates apoptosis and radiation sensitization in lung cancer cell lines A549 and H460 via the SirT1/NF-κB/Smac pathway.

Background/Aims: Circular RNAs (circRNAs) make up a large class of non-coding RNAs and play important roles in a variety of diseases, including nervous system diseases and cancers. The intestinal epithelium is sensitive to ionizing radiation, radiotherapy of abdominal or pelvic tumors or nuclear accident exposure can lead to high radiation toxicity, which can result in radiation-induced intestinal injury. The goal of this present study was to analyze the potential roles of circRNAs in radiation-induced intestinal injury. Methods: Mice were divided into two groups: control group and irradiated group. Irradiated group was 3.5 days after 14Gy abdominal irradiation (ABI) group. We started with RNA-seq of circRNA changes in mouse jejuna after radiation and validated by RT-PCR in the following experimental. miRNAs targeted mRNAs were predicted using proprietary software based on target scan and Miranda. The network of circRNA-miRNA-mRNA was illustrated by cytoscape software. Results: 2751 circRNAs were detected in the two groups. At day 3.5 post-radiation, 42 and 48 circRNAs were found to be significantly upregulated and downregulated, respectively, compared to the control (p≤0.05, Fold Change ≥2). Further, the altered expression of 10 circRNAs (chr18: 35610871-35613502+, chr15: 95864225-95894541+, chr3: 96041338-96042928-, chr5: 64096979-64108263+, chr19: 16705875-16710941-, chr5: 134491893-134500149-, chr19: 42562552-42564341+, chr5: 32640331-32664400+, chr3: 72958113-72960367- and chr8: 79343654-79372364-) were verified by RT-PCR. Compared the miRNA-targeted mRNAs with our mRNAs sequencing data, we found 14 upregulated circRNA-targeted mRNAs were also unregulated and 22 downregulated circRNAs-targeted mRNAs were also downregulated. Gene ontology and KEGG pathway analyses indicated the predicted genes were mainly involved in the MAPK signaling pathway. Conclusions: This study reveals that expression of circRNAs was altered in the jejuna of mice post-irradiation and provides a resource for the study of circRNAs in radiation-induced intestinal injury and repair.

In this data article, 146 villagers (exposed group) were randomly selected from the workers who involved in the e-wastes recycling directly as a daily job in Tianjin. Control group, including 121 villagers, came from another town without e-waste disposal sites. Chromosomal aberrations (CA) and cytokinesis blocking micronucleus (CBMN) were performed to detect the cytogenetic effect for each subject. DNA damage was detected using comet assay; the DNA percentage in the comet tail (TDNA%), tail moment (TM), and Olive tail moment (OTM) were recorded to describe DNA damage to lymphocytes and spermatozoa. Routine semen analysis, spermatozoa motility and morphology were analyzed. The RT2Profiler PCR array was used to measure levels of expression of 84 genes related to quality of DNA. It showed significant relationships between CA, CBMN, DNA damage and exposure time in exposure subjects. The alteration of sperm motility rate, abnormality rate and total sperm counts had association with exposure time and age.

Human are exposed to ionizing radiation from natural and artificial sources, which consequently poses a possible risk to human health. However, accumulating evidence indicates that the biological effects of low-dose radiation (LDR) are different from those of high-dose radiation (HDR). Low-dose radiation–induced hormesis has been extensively observed in different biological systems, including immunological and hematopoietic systems. Adaptive responses in response to LDR that can induce cellular resistance to genotoxic effects from subsequent exposure to HDR have also been described and researched. Bystander effects, another type of biological effect induced by LDR, have been shown to widely occur in many cell types. Furthermore, the influence of LDR-induced biological effects on certain diseases, such as cancer and diabetes, has also attracted the interest of researchers. Many studies have suggested that LDR has the potential antitumor and antidiabetic complications effects. In addition, the researches on whether LDR could induce stochastic effects were also debated. Studies on the biological effects of LDR in China started in 1970s and considerable progress has been made since. In the present article, we provide an overview of the research progress on the biological effects of LDR in China.

Radiation therapy is one of the most common cancer treatments. It is important to understand how cells respond to ionizing radiation (IR) to improve therapeutic efficacy. Circular RNAs (circRNAs) recently have been found to regulate a variety of cellular processes. However, it is poorly defined that their expression pattern and their identity in cells following IR exposure. Here, we performed high-throughput sequencing and comprehensive analysis of circRNA expression in human embryonic kidney (HEK) 293T cells before and after irradiation. We identified totally 5592 circRNAs and discovered 1038 new circRNAs. We found 158 circRNAs with significantly differential expression after IR exposure. Among them, there were 61 upregulated and 97 downregulated circRNAs. Using Gene Ontology, Kyoto Encyclopedia of Genes and Genomes pathway, and circRNA-microRNA-messenger RNA network analyses, we found the differentially expressed circRNAs might be involved in the signal pathways of oxidative phosphorylation, epithelial growth factor receptor (EGFR) tyrosine kinase inhibitor resistance, and mammalian target of rapamycin (mTOR) signaling.

The planting area of macadamia in China accounted for more than one third of the world’s planted area. The lipid compositions, minor components, and antioxidant capacities of fifteen varieties of macadamia oil (MO) in China were comparatively investigated. All varieties of MO were rich in monounsaturated fatty acids, mainly including oleic acid (61.74–66.47%) and palmitoleic acid (13.22–17.63%). The main triacylglycerols of MO were first time reported, including 19.2–26.1% of triolein, 16.4–18.2% of 1-palmitoyl-2,3-dioleoyl-glycerol, and 11.9–13.7% of 1-palmitoleoyl-2-oleoyl-3-stearoyl-glycerol, etc. The polyphenol, α-tocotrienol and squalene content varied among the cultivars, while Fuji (791) contained the highest polyphenols and squalene content. Multiple linear regression analysis indicated the polyphenols and squalene content positively correlated with the antioxidant capacity. This study can provide a crucial directive for the breeding of macadamia and offer an insight into industrial application of MO in China.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Background and objective The curative effect of radiotherapy may be limited by the radioresistance of tumor. Mimetic compounds of Second mitochondria-derived activator of caspase (Smac) were hopeful to become new drugs of radiosensitization for tumor because they can increase radiation induced apoptosis in tumor cells. The aim of present study is to observe the radiosensitization effect of a new Smac mimetic ANTP-SmacN7 fusion peptide in H460 cell line. Methods In order to observe if the fusion peptide can enter into tumor cell, ANTP-SmacN7 fusion peptide was synthesized and linked by FITC. H460 cell was divided into control, radiation only, ANTP-SmacN7 only and ANTP-SmacN7 combined with radiation group. The cells were exposed by 0, 2, 4 and 6 Gy and the concentration of ANTP-SmacN7 was 20 μmol/L. Proliferation of H460 tumor cell was detected by WST-1 assay. There are four groups in the present study: control group, radiation group, ANTP-SmacN7 group and ANTP-SmacN7 combined with radiation group. Apoptosis was detected by flow cytometry at 24 and 48 hours after the treatment of all the groups. The level of caspase3 and cleaved caspase3 were detected by Western blot assay. Results ANTP-SmacN7 can enter into cells and promote the radiosensitization of H460 cell obviously (F=25.1, P

The proteasome inhibitor is a target therapy for multiple myeloma (MM) patients, which has increased the overall survival rate of multiple myeloma in clinic. However, relapse and toxicity are major challenges for almost all MM patients. Thus, there is an urgent need for an effective and less toxic combination therapy. Here, we demonstrated that a natural compound, resveratrol (RSV) displayed anti-proliferative activity in a dose- and time-dependent manner in a panel of MM cell lines. More importantly, a low concentration of RSV was synergistic with a low dose of the proteasome inhibitor carfilzomib (CFZ) to induce apoptosis in myeloma cells. Further studies showed that mitochondria was a key regulatory site after RSV/CFZ combination treatment. RSV induced the release of second mitochondria-derived activator of caspase (Smac) in a dose-dependent manner and kept the Smac in a high level after combination with CFZ. Also, RSV was additive with CFZ to increase reactive oxygen species (ROS) production. Moreover, a stress sensor SIRT1, with deacetylase enzyme activity, was remarkably downregulated after RSV/CFZ combination, thereby significantly decreasing its target protein, survivin in MM cells. Simultaneously, autophagy was invoked after RSV/CFZ combination treatment in myeloma cells. Further inhibition of autophagy could increase more ROS production and apoptosis, indicating a close linkage between autophagy and proteasome to modulate the oxidative stress. Together, these findings suggest that induction of multiple stress responses after RSV/CFZ combination is a major mechanism to synergistically inhibit MM cell growth and reduce the toxicity of CFZ in MM cells. This study also provides an important rationale for the clinic to consider an autophagy inhibitor for the combination therapy in MM patients.