Amentoflavone attenuates cell proliferation and induces ferroptosis in human gastric cancer by miR-496/ATF2 axis.

Amentoflavone (AF) is a natural multifunctional biflavonoid that has been revealed to possess multiple biological activities, including anticancer activity. Here, this work focused on exploring the functions and mechanism of AF in gastric cancer (GC). Levels of genes and proteins were examined by quantitative real-time PCR and western blotting. Cell proliferation and cell death were analyzed using cell counting kit-8, colony formation, and lactate dehydrogenase (LDH) release assay, respectively. Cell ferroptosis was evaluated by detecting the levels of malondialdehyde (MDA), reduced glutathione (GSH), Fe2+ , and intracellular reactive oxygen species (ROS). The binding between miR-496 and activating transcription factor 2 (ATF2) was confirmed by using dual-luciferase reporter assay. Murine xenograft assay was conducted for in vivo experiments. The results showed that AF suppressed the proliferation and induced ferroptotic cell death in GC cells. MiR-496 expression was decreased in GC tissues and cells, and AF treatment increased miR-496 expression level in GC cells. Functionally, miR-496 inhibition reversed the inhibitory effects of AF on GC cell proliferation and promoting effects on ferroptotic cell death. Mechanistically, ATF2 was targeted by miR-496. ATF2 expression was increased in GC tissues and cells, which was decreased by AF treatment and subsequently rescued by miR-496 downregulation in GC cells. Moreover, miR-496 overexpression suppressed the proliferation and induced ferroptotic cell death in GC cells via targeting ATF2. In all, AF suppressed the proliferation and induced ferroptotic cell death in GC cells via miR-496/ATF2 axis, indicating a novel therapeutic approach for GC patients.

Effectiveness and safety of mono-anlotinib mono therapy or in combination with chemotherapy in platinum-resistant recurrent ovarian cancer: a single-center retrospective study.

OBJECTIVE: To evaluate the clinical efficacy of mono-anlotinib therapy by itself or in combination with chemotherapy in platinum-resistant recurrent ovarian cancer (PROC). METHODS: The clinical data of 35 patients with platinum-resistant recurrent ovarian cancer admitted to the First Affiliated Hospital of Anhui Medical University from March 2019 to July 2020 were retrospectively analyzed. All the patients received anlotinib mono- or combined chemotherapy. The effectiveness and adverse events (AEs) were analyzed by RECIST1.1 and CTCAE5.0. RESULTS: In the 35 patients, the median follow-up was 9.80 (95% CI: 3.83-15.77) months. The median progression free survival (mPFS) achieved 6.50 (95% CI: 2.02-10.98) months, the objective response rate (ORR) achieved 17.14%, and disease control rate (DCR) achieved 60.00%. ORR and DCR were 12.50% and 25.0% for monotherapy, 18.52% and 70.37% for combined chemotherapy. The PFS of combined chemotherapy was longer than that of monotherapy (log-rank P = 0.003). thirty-four patients (97.14%) were in a third-line therapy or above, and their ORR and DCR were 14.71% and 58.82%, respectively. Two patients discontinued treatment because of intolerable AEs. No cases of grade 4-5 AEs have been reported. CONCLUSION: Anlotinib had promising effectiveness and tolerable safety in patients with PROC, even in patients who accepted anlotinib as a third-line or above therapy or with a history of other antiangiogenic drugs.

A novel damage identification method for flue gas turbine blades based on tip timing.

Tip timing signal analysis has been applied to the online condition monitoring of high-speed blades. However, traditional tip timing analysis methods are not suitable for low-speed flue gas turbines. Therefore, this paper proposes a novel blade tip timing signal analysis method based on an investigation of the dynamic response characteristics of low-speed blades. First, the finite element modal theory is introduced to analyze the characteristics of blade damage. Second, an equivalent cantilever beam analysis model of flue gas turbine blades is established under complex environment and working conditions. In order to monitor the variation of local stiffness, a damage identification method based on the variation of the free end deflection of the equivalent cantilever beam is proposed. Finally, a rotating blade tip timing monitoring testing rig is established to verify the feasibility of the proposed method. The results show that the cracks originating at about 80% of the blade height have the greatest influence on blade stiffness, followed by blade root. The calculated blade damage parameters are 4.8464 mm and 3.7588 mm, and the crack influencing factors are 4.7476 and 3.6822, respectively, indicating that the change trend is consistent with the blade damage rules.

Bacillamide F, Extracted from Marine Bacillus atrophaeus C89, Preliminary Effects on Leukemia Cell Lines.

Developing new treatments for leukemia is essential since current therapies often suffer from drug resistance and toxicity. Bacillamides are very promising, naturally occurring compounds with various bioactivities. In the present study, we investigated the use of bacillamide analogues, a new thiazole alkaloid bacillamide F that was isolated from marine Bacillus atrophaeus C89 associated with sponge Dysidea avara. The structure of the new compound bacillamide F with indolyl−thiazolyl−pyrrolidine ring was determined by high resolution mass spectrometry, secondary mass spectrometry, and nuclear magnetic resonance analyses. Intriguingly, bacillamide F is able to inhibit the proliferation of an acute myeloid leukemia cell line HL60 (IC50 (24 h) 21.82 µM), and an acute T-cell leukemia Jurkat (IC50 (24 h) 46.90 µM), rather than inhibit the proliferation of the acute histiocytic lymphoma U-937 cell line, human fetal lung fibroblast MRC-5 cell line, and some solid tumor cell lines (IC50 (24 h) > 100 µM). The study provides a new indication of the pharmacological activity of natural product bacillamides.

The cuproptosis-related gene signature serves as a potential prognostic predictor for ovarian cancer using bioinformatics analysis.

Background: Studies have shown that copper is involved in the tumorigenesis and development of ovarian cancer. In this work, we aimed to build a prognostic classification system associated with cuproptosis to predict ovarian cancer prognosis. Methods: Information of ovarian cancer samples were acquired from The Cancer Genome Atlas (TCGA)-ovarian cancer and GSE26193 dataset. Cuproptosis-related genes were screened from previous research. ConsensusClusterPlus was applied to determine molecular subtypes, which were evaluated by tumor immune microenvironment analysis, TIDE algorithm, and functional enrichment analysis. Furthermore, limma analysis and univariate Cox analysis were used to construct a cuproptosis-related prognostic signature for ovarian cancer. Univariate and multivariate Cox regression analyses were used to analyze the independence of clinical factors and model. Results: A total of 15 genes related to cuproptosis were identified, and 2 clusters (C1 and C2) were determined. C1 had a better survival outcome, less advanced stage, enhanced immune infiltration, was more sensitive to immunotherapy, and showed enrichment in tricarboxylic acid (TCA)-related pathways. An 8 cuproptosis-associated gene signature was constructed, and the signature was verified in the GSE26193 dataset. A higher risk score of the cuproptosis-related gene signature was significantly correlated with worse overall survival (OS) (P<0.0001), which was validated in GSE26193 dataset successfully. Cox survival analysis showed that risk score was an independent predictor [hazard ratio (HR) =2.66, P<0.001]. Functional enrichment and tumor immune microenvironment analyses showed that high-risk patients tended to have immunologically sensitive tumors. Conclusions: The cuproptosis-related gene signature may serve as a potential prognostic predictor for ovarian cancer patients and may offer novel treatment strategies for ovarian cancer.

Icariin Regulates the hsa_circ_0003159/eIF4A3/bcl-2 Axis to Promote Gastric Cancer Cell Apoptosis.

Objective: To clarify the mechanism of icariin (ICA) promoting gastric cancer (GC) cell apoptosis by regulating circ_0003159/eIF4A3/bcl-2 axis. Methods: The mRNA or protein levels were detected by qRT-PCR or the western blot. The interaction between eIF4A3 protein and circ_0003159 or eIF4A3 protein and bcl-2 mRNA were validated by RNA pull down assays and the RNA immunoprecipitation (RIP) assay. The cell viability was measured by the cell counting kit (CCK)-8 kit. The cell apoptosis was measured by flow cytometry. Results: Compared with the group Vector, the ratio of cytoplasmic eIF4A3/nuclear eIF4A3 in the cell with circ_0003159 overexpression was significantly higher. RIP and RNA pull down results proved the interaction between eIF4A3 and circ_0003159. The RIP assay further validated the interaction between eIF4A3 and bcl-2. By gain or loss of the functional experiment, hsa_circ_0003159 was proved to recruit eIF4A3 to inhibit bcl-2 expression. Hsa_circ_0003159 regulates eIF4A3/bcl-2 to reduce GC cell viability and increase apoptosis Furthermore, ICA regulates hsa_circ_0003159/eIF4A3/bcl-2 axis to inhibit GC cell activity and induce GC cell apoptosis in vitro. Conclusion: These data showed that ICA could effectively reduce the GC cell activity and induce GC cell apoptosis via hsa_circ_0003159/eIF4A3/bcl-2 axis, which provides new theoretical evidence for the treatment of GC by ICA.

Icariin inhibits gastric cancer cell growth by regulating the hsa_circ_0003159/miR-223-3p/NLRP3 signaling axis.

This study aimed to clarify the expression and role of hsa_circ_0003159 in gastric carcinogenesis, and validate the protective effects of Icariin (ICA) against gastric cancer (GC) cell growth through the in vitro and in vivo experiments. The levels of hsa_circ_0003159, microRNA (miR)-223-3p and NLRP3 were measured by Quantitative real time Polymerase Chain Reaction or western blot. The cell counting kit (CCK)-8 was used to determine cell proliferation. The target relationship of miR-223-3p/hsa_circ_0003159 and miR-223-3p/NLRP3 was predicted by bioinformatics and validated by the dual-luciferase reporter and pull-down assays. Xenograft model was constructed to assess the roles of hsa_circ_0003159 and protective effects of ICA in GC in vivo. Results showed that hsa_circ_0003159 was downregulated in GC cell lines and its overexpression promoted GC cell viability. MiR-223-3p was identified as a target of hsa_circ_0003159. By competitively sponging miR-223-3p, hsa_circ_0003159 positively regulated NLRP3 expression. MiR-223-3p mimics reversed the suppressive effect of hsa_circ_0003159 on GC cell viability and cell pyroptosis. Importantly, ICA inhibited GC cell viability and triggered GC cell pyroptosis by regulating the hsa_circ_0003159/miR-223-3p/NLRP3 axis in vitro and in vivo. In conclusion, this study indicated ICA inhibits GC cell growth by regulating the hsa_circ_0003159/miR-223-3p/NLRP3 signaling axis. This study not only reveals the mechanism of gastric carcinogenesis but also provides potential molecular targets and therapeutic tools for its treatment.

Study on Mechanism of Yiqi Yangyin Jiedu Recipe Inhibiting Triple Negative Breast Cancer Growth: A Network Pharmacology and In Vitro Verification.

Background: The present study explores the potential mechanism of Yiqi yangyin jiedu Recipe (YQYYJDR) on triple negative breast cancer via adopting network pharmacology and experimental validation. Materials and Methods: The potential active compounds and target genes of YQYYJDR were screened out from TCMSP database with OB ≥ 30% and DL index ≥ 0.18. The potential pathways and function enrichment were identified from Metascape website. MDA-MB-231 and MDA-MB-468 cells were tested for cell viability, invasion, and apoptosis by in vitro and in vivo experiments. Results: A total of 153 bioactive compounds and 281 target genes of YQYYJDR were retrieved from TCMSP database. The top 5 enrichment pathways of YQYYJDR target genes include pathways in cancer, AGE-RAGE signaling pathway in diabetic complications, proteoglycans in cancer, IL-17 signaling pathway, and platinum drug resistance. 65 target genes were included in the pathway of cancer. Biological function enrichment analysis of 65 genes showed YQYYJDR inhibited tumor growth mainly through apoptotic pathway. In vitro experiments showed that YQYYJDR could inhibit the proliferation and invasion of MDA-MB-231 and MDA-MB-468 cells, arrest cells in S stage, and induce cell apoptosis. YQYYJDR upregulated BAX, caspase3, and cleaved caspase3 expression and downregulated BCL2 expression. In vivo experiments showed that YQYYJDR could inhibit tumor growth. Conclusions: In this study, network pharmacology and experiment were used to explore the mechanism of YQYYJDR on triple negative breast cancer. In vitro and in vivo experiments showed that YQYYJDR could inhibit the growth of triple negative breast cancer and induce cell apoptosis. Apoptosis pathway plays a significant role in the treatment of triple negative breast cancer.

Two-color fluorescent proteins reporting survivin regulation in breast cancer cells for high throughput drug screening.

Reporter gene assay is widely used for high throughput drug screening and drug action mechanism evaluation. In this study, we developed a robust dual-fluorescent reporter assay to detect drugs repressing the transcription of survivin, a cancer biomarker from the inhibitor of apoptosis family, in breast cancer cells cultured in three-dimensional (3D) microbioreactors. Survivin is overexpressed in numerous malignancies but almost silent in normal tissue cells and is considered a lead target for cancer therapy. Breast cancer MCF-7 cells were engineered to express enhanced green fluorescent protein driven by a survivin promoter and red fluorescent protein driven by a cytomegalovirus promoter as internal control to detect changes in survivin expression in cells as affected by drugs. This 3D dual-fluorescent reporter assay was validated with YM155 and doxorubicin, which were known to downregulate survivin in cancer cells, and further evaluated with two widely used anticancer compounds, cisplatin, and epigallocatechin gallate, to evaluate their effects on survivin expression. The results showed that the 3D dual-fluorescent reporter assay was robust for high throughput screening of drugs targeting survivin in breast cancer cells.

Surface-Displayed Amuc_1100 From Akkermansia muciniphila on Lactococcus lactis ZHY1 Improves Hepatic Steatosis and Intestinal Health in High-Fat-Fed Zebrafish.

Fatty liver and intestinal barrier damage were widespread in most farmed fish, which severely restrict the development of aquaculture. Therefore, there was an urgent need to develop green feed additives to maintain host liver and intestinal health. In this study, a probiotic pili-like protein, Amuc_1100 (AM protein), was anchored to the surface of Lactococcus lactis ZHY1, and the effects of the recombinant bacteria AM-ZHY1 on liver fat accumulation and intestinal health were evaluated. Zebrafish were fed a basal diet, high-fat diet, and high-fat diet with AM-ZHY1 (108 cfu/g) or control bacteria ZHY1 for 4 weeks. Treatment with AM-ZHY1 significantly reduced hepatic steatosis in zebrafish. Quantitative PCR (qPCR) detection showed that the expression of the lipogenesis [peroxisome-proliferator-activated receptors (PPARγ), sterol regulatory element-binding proteins-1c (SREBP-1c), fatty acid synthase (FAS), and acetyl-CoA carboxylase 1 (ACC1)] and lipid transport genes (CD36 and FABP6) in the liver were significantly downregulated (p < 0.05), indicating that AM-ZHY1 could reduce liver fat accumulation by inhibiting lipid synthesis and absorption. Moreover, supplementing AM-ZHY1 to a high-fat diet could significantly reduce serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels, indicating that liver injury caused by high-fat diets was improved. The expression of tumor necrosis factor (TNF)-a and interleukin (IL)-6 in the liver decreased significantly (p < 0.05), while IL-1ß and IL-10 did not change significantly in the AM-ZHY1 group. Compared to the high-fat diet-fed group, the AM-ZHY1 group, but not the ZHY1 group, significantly increased the expression of intestinal tight junction (TJ) proteins (TJP1a, claudina, claudin7, claudin7b, claudin11a, claudin12, and claudin15a; p < 0.05). Compared to the high-fat diet group, the Proteobacteria and Fusobacteria were significantly reduced and increased in the AM-ZHY1 group, respectively. In conclusion, the recombinant bacteria AM-ZHY1 has the capacity to maintain intestinal health by protecting intestinal integrity and improving intestinal flora structure and improving fatty liver disease by inhibiting lipid synthesis and absorption. This study will lay a foundation for the application of AM protein in improving abnormal fat deposition and restoring the intestinal barrier in fish.

Rare complication of acute adrenocortical dysfunction in adrenocortical carcinoma after transcatheter arterial chemoembolization: A case report.

BACKGROUND: Adrenocortical carcinoma (ACC) is a rare and highly invasive endocrine malignant tumor with a poor prognosis. Although surgical resection is the main treatment for ACC, postoperative recurrence and metastasis have become the important factors of death. Transcatheter arterial chemoembolization (TACE) is an important option for the treatment of advanced ACC with liver metastasis. However, due to the small number of patients treated for ACC, the safety of the operation is not completely clear and needs to be further studied. CASE SUMMARY: A 47-year-old patient with ACC after surgery was admitted for reexamination by abdominal computerized tomography suggesting liver metastasis. Because the patient expressed reluctance to undergo surgery again, we treated her with TACE for the liver lesions. After treatment, symptoms of acute adrenal dysfunction such as decreased blood pressure, anorexia, and fatigue appeared, which were relieved after hydrocortisone treatment. To date, the patient's liver lesion is well controlled and no other metastases are observed. CONCLUSION: We report a rare case of acute adrenal hypofunction after TACE. Glucocorticoid supplementation can alleviate the symptoms.

Apatinib combined with Keytruda treatment induces apoptosis of gastric carcinoma cells through CES4/miR-616-5p/DUSP2 axis.

Gastric carcinoma (GC) is a highly malignant and heterogeneous tumour. Long non-coding RNA CES4 is down-regulated in GC. However, whether CES4 can participate in GC remains unclear; we have carried out research on this topic. GC cells (HGC-27 and MKN-7) were treated with anti-tumour drugs: apatinib combined with Keytruda. Cell viability and apoptosis were detected by CCK-8 assay and flow cytometry. Gene and protein expression were examined by quantitative real-time PCR and western blot. Luciferase reporter assay was performed to verify the relationship among CES4, miR-616-5p and dual-specificity phosphatase-2 (DUSP2). CES4 was highly expressed in the apatinib combined with Keytruda-treated HGC-27 and MKN-7 cells. Apatinib combined with Keytruda treatment repressed cell viability and promoted apoptosis of HGC-27 and MKN-7 cells, which was abrogated by CES4 knockdown. Furthermore, CES4 promoted DUSP2 expression by sponging miR-616-5p in HGC-27 and MKN-7 cells. CES4 knockdown promoted cell viability and inhibited apoptosis of drug-treated HGC-27 and MKN-7 cells by regulating miR-616-5p/DUSP2 axis. In conclusion, these data demonstrate that apatinib combined with Keytruda treatment induces apoptosis of GC cells through CES4/miR-616-5p/DUSP2 axis. Thus, this work provides the experimental basis for the combination of apatinib and Keytruda as a treatment for GC.

Retracted: Anticancer Activity of Metformin, an Antidiabetic Drug, Against Ovarian Cancer Cells Involves Inhibition of Cysteine-Rich 61 (Cyr61)/Akt/Mammalian Target of Rapamycin (mTOR) Signaling Pathway.

An editorial decision has been made to retract this manuscript due to breach of publishing guidelines, following the identification of non-original and manipulated figures. Reference: Fengli Zhang, Huixiao Chen, Jing Du, Bin Wang, Lixiao Yang: Anticancer Activity of Metformin, an Antidiabetic Drug, Against Ovarian Cancer Cells Involves Inhibition of Cysteine-Rich 61 (Cyr61)/Akt/Mammalian Target of Rapamycin (mTOR) Signaling Pathway. Med Sci Monit 2018; 24: 6093-6101. 10.12659/MSM.909745.

A specific selenium-chelating peptide isolated from the protein hydrolysate of Grifola frondosa.

Background: Grifola frondosa is a type of edible medicinal mushroom with abundant proteins. Selenium (Se) is an essential micronutrient for human. Many animal experiments and clinical studies had indicated that Se plays an important role in diverse physiologic actions. Most inorganic selenium compounds are toxic, and the lowest lethal dose is relatively small. Peptide-Se chelate can probably be dietary supplements in functional foods for humans with Se deficiency. Methods: In this study, a specific tripeptide Arg-Leu-Ala (RLA) with strong Se-chelating capacity was purified from Grifola frondosa through ultrafiltration, reversed-phase HPLC and gel filtration chromatography. The UV, SEM, XRD, 1H NMR spectra are shown to provide more information about characterization of RLA-Se chelates. The bioavailability of RLA-Se chelate in Caco-2 cell line was investigated by using human colon cancer Caco-2 cells as model. iTRAQ comparative proteomics approach were used to identify the differentially expressed proteins. Results: The Se binding capacity of RLA was 84.47 ± 1.21 mg g-1. The results of UV, X-ray diffraction (XRD), 1H NMR and SEM structure analysis showed that the binding of selenium in the hydrolysate of Grifola frondosa protein was successful, and the amino and carboxyl groups of RLA were involved in the coordination of Se, which was the main site of chelation. The results of absorption of RLA-Se chelate in Caco-2 cells showed that RLA-Se chelate could be used as selenium supplement source. Using iTRAQ comparative proteomics approach, 40 proteins found significant. RLA-Se treatment had been demonstrated to present a higher accumulation of Se compared with control treatment and show an effective absorption by Caco-2 with the result that E3 protein performed up regulation. RLA-Se may play roles in cell cycle and apoptosis as an essential micronutrient. To sum up, our research results show that Grifola polypeptide-Se chelate is a promising multifunctional organic selenium product, which can be used as a new functional supplement for selenium deficiency.

Treatment effect of apatinib combined chemotherapy as second-line or above therapy in patients with advanced gastric cancer or adenocarcinoma of the gastroesophageal junction.

This study aimed to compare the therapeutic effects between apatinib combined chemotherapy and chemotherapy alone as second-line or above therapy in advanced gastric cancer (GC) or adenocarcinoma of the gastroesophageal junction (AGEJ). The clinical data of advanced GC or AGEJ patients, including sex, age, Eastern Cooperative Oncology Group (ECOG) grading, chemotherapy regimen, pathological grading, location of primary lesion, previous gastrectomy, metastases, previous chemotherapy or radiotherapy were retrospectively collected, and the progression-free survival (PFS) was recorded. 127 patients underwent apatinib combined chemotherapy and 60 patients underwent chemotherapy regimen alone. Disease control rate (DCR) of patients with apatinib combined chemotherapy was higher than that of chemotherapy alone (P=0.033). A Kaplan-Meier (KM) plot showed that PFS was significantly longer in patients receiving apatinib combined chemotherapy than those treated by chemotherapy alone (P = 0.002). The PFS of patients with a number of metastatic lesions ≤ 2 was obviously longer than that of patients with a number of metastatic lesions > 2 (P < 0.001). Cox regression analysis revealed that PFS was independently associated with the number of metastatic lesions >2 (HR=2.129, 95% CI: 1.256-3.608, P=0.005) and treatment methods (chemotherapy alone or apatinib combined chemotherapy) (HR=1.427, 95% CI: 1.055-1.930, P=0.021). Compared with chemotherapy alone, apatinib combined chemotherapy could significantly improve DCR and prolong the PFS in advanced GC or AGEJ cases who had failed in at least first-line chemotherapy with acceptable tolerance.

Bioinformatics analysis and characterization of a secretory cystatin from Thelohanellus kitauei.

Thelohanellus kitauei, is a member of obligate parasitic myxozoans, which causes intestinal giant-cystic disease of common carp (Cyprinus carpio) and has resulted in significant economic losses in carp farms. Cystatin secreted by parasites can regulate the immune response of host to facilitate parasite's survival. In this study, the secretory TK-cystatin gene, encoding a protein of 120 amino acid residues (13.65 kDa), was cloned from T. kitauei genome. Phylogenetic analysis showed that TK-cystatin gene is closely related to the cystatin-A from Hydra vulgaris. Multiple sequence alignment revealed that TK-cystatin had three conserved motifs: N-terminal G19G20, Q73VVAG77, and C-terminal L102P103. Molecular docking between TK-cystatin and three cysteine proteases showed a lower binding energy (- 13 KJ/mol) with cathepsin L whereas a higher binding energy (- 8.6 KJ/mol) with cathepsin B. TK-cystatin gene was expressed in Escherichia coli. Activity assays revealed that TK-cystatin has stronger inhibitory activity on endopeptidases (papain and cathepsin L) and weaker inhibitory activity on exopeptidase (cathepsin B). TK-cystatin was stable under the condition of acidity or alkalinity or below 57 °C. This study laid a foundation for the design and development of the anti-T. kitauei vaccine in carp culture in the future.

CD73 Blockade Promotes Dendritic Cell Infiltration of Irradiated Tumors and Tumor Rejection.

The ability of focal radiotherapy to promote priming of tumor-specific CD8+ T cells and increase responses to immunotherapy is dependent on infiltration of the tumor by Batf3-dependent conventional dendritic cell type 1 (cDC1) cells. Such infiltration is driven by radiotherapy-induced IFN type I (IFN-I). Other signals may also modulate cDC1 infiltration of irradiated tumors. Here we found increased expression of adenosine-generating enzymes CD38 and CD73 in irradiated mouse and human breast cancer cells and increased adenosine in mouse tumors following radiotherapy. CD73 blockade alone had no effect. CD73 blockade with radiotherapy restored radiotherapy-induced cDC1 infiltration of tumors in settings where radiotherapy induction of IFN-I was suboptimal. In the absence of radiotherapy-induced IFN-I, blockade of CD73 was required for rejection of the irradiated tumor and for systemic tumor control (abscopal effect) in the context of cytotoxic T-lymphocyte-associated protein 4 blockade. These results suggest that CD73 may be a radiation-induced checkpoint, and that CD73 blockade in combination with radiotherapy and immune checkpoint blockade might improve patient response to therapy.

Heavy metal pollution and health risk assessment of agricultural soil near a smelter in an industrial city in China.

To assess heavy metal pollution and human health risk, a total of 28 topsoil samples were collected during four seasons from seven agricultural soil sites near a famous smelter in Jiyuan, China. The maximum concentrations of Cd, Pb, Hg, As, Zn, Cu, Ni, and Cr were 26.00, 2601.00, 3.29, 65.00, 410.00, 156.30, 54.80, and 73.60 mg kg-1, respectively. Compared with the sampling site nearest to the smelter, the concentrations of six metals at the farthest site were decreased significantly (P < 0.05). All sites were heavily contaminated, with Nemerow index (P) >3.0, and all sites had very high ecological risks related to Cd and Hg. The non-carcinogenic risk for children (based on combined exposure to the eight metals) was above the safety level. The carcinogenic risk of As for adults (8.98 × 10-6) and children (1.49 × 10-5) exceeded the acceptable level (1 × 10-6). Results suggest a serious health risk in the polluted areas, particularly for children.Abbreviation Cd: Cadmium; Pb: Lead; Hg: Mercury; As: Arsenic; Zn: Zinc; Cu: Copper; Ni: Nickel; Cr: Chromium; P: Nemerow index; RI: Potential ecological risk index; Ei: Monomial potential ecological risk of a specific heavy metal; HI: non-carcinogenic hazard index; CR: Carcinogenic risk; TN: Total nitrogen; TP: Total phosphorus; OM: Organic matter; MC: Moisture content; ADD: Average daily dose.

MicroRNA-103 regulates the progression in endometrial carcinoma through ZO-1.

Endometrial carcinoma (EC) is one of the most common gynecological cancers in many developing countries. Although tremendous advances have been made in the diagnosis and treatment of EC, there is still no adequate biomarker currently available for predicting the prognosis of this cancer. In this study, we found that miR-103 expression was significantly upregulated in EC tissues than their paired non-carcinoma tissues. Overexpression of miR-103 significantly promoted EC cell proliferation, while downregulation of miR-103 significantly suppressed EC cell proliferation. In addition, ZO-1 expression was significantly downregulated in the EC tissues than their paired non-carcinoma tissues. We also found an inverse correlation between ZO-1 and miR-103. Moreover, ZO-1 was validated as the direct target of miR-103. The downregulation of ZO-1 significantly enhanced EC cell proliferation. In conclusion, miR-103 could regulate EC cell proliferation through directly targeting ZO-1. Our results provide a potential development of microRNA-based targeted approaches for the treatment of EC.