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BACKGROUND This study explored the levels and prognostic value of ischemia modified albumin (IMA), red blood cell distribution width (RDW), and lipoprotein (LP) in patients with diabetes melltus (DM) complicated withcoronary heart disease (CHD). METHODS A total of 95 patients with DM who were diagnosed and treatedfrom January 2018 to January 2019 were retrospectively analyzed. All included patients underwent percutaneous coronary intervention (PCI). Patients with DM complicated with CHDwere designated group A (n=61) and patients without CHD complications were designated group B (n=34). During the same period, 45 patients without DM who underwent physical examination in our hospital were included as a control group.The levels of IMA, LP, and RDW in the 3 groups of patients were compared. The study examined the occurrence of cardiovascular events after PCI treatment in patients with DM complicated with CHD, and the related risk factors were assessed using multivariate logistic regression analysis. Furthermore, the receiver operating characteristic (ROC) curve was used to analyze the value of IMA, LP, and RDW in predicting cardiovascular events in DM patients complicated with CHD. RESULTS The levels of IMA, LP, and RDW werehigher in groups A and B compared to the control group (P

Context Ursolic acid (UA), a natural product, shows a broad spectrum of anticancer effects. However, the poor bioavailability and efficacy of UA limit its clinical application. Objective We developed novel analogues of UA with enhanced antitumor activities by the extensive chemical modification of UA. Materials and methods We developed multiple compounds by structural modification of UA, and found that UA232 had stronger activity than UA. The effects of UA232 (0–50 μM) on inhibiting the proliferation of A549 and H460 cells were determined by CCK-8 for 24, 48, or 72 h. The proapoptotic effect of UA232 was analyzed by microscopy and flow cytometry, and the potential signal pathway affected by UA232 was further validated by Western blotting and flow cytometry. Results Compared with UA, UA232 showed a stronger ability to inhibit the proliferation of lung cancer cells (IC50 = 5.4–6.1 μM for A549 and 3.9–5.7 μM for H460 cells). UA232 could induce not only cell cycle arrest in the G0/G1 phase but also apoptosis in both A549 and H460 cells. The treatment of UA232 could lead to an increase of CHOP expression rather than an increase in Bax or caspase-8, indicating that the apoptosis induced by UA232 was correlated with the endoplasmic reticulum stress (ER stress) pathway. Treatment with the ER stress-specific inhibitor, 4-PBA, decreased the ability of UA232 to induce apoptosis in A549 and H460 cells. Conclusion UA232 induced apoptosis through the ER stress pathway, and showed stronger growth-inhibitory effects in A549 and H460 cells compared to UA, which may be a potential anticancer drug to suppress the proliferation of lung cancer.

Previous studies suggested that serine can promote the synthesis of selenoproteins and the interaction, transformation, and replacement of serine, cysteine, and selenocysteine have been observed in the human body. This study was designed to clarify whether the dietary intakes of serine and sulfate-containing amino acids (SAAs) could directly affect the selenium (Se) nutritional status or the level of milk Se in lactating women. Breast milk and plasma samples were collected from a total of 264 lactating Chinese women when they revisited their local hospital at the 42nd day postpartum to detect the concentration of Se with ICP-MS and the content of selenoprotein P (SEPP1) and the activity of glutathione peroxidase 3 (GPX3) in the plasma by ELISA. The daily Se intake by each subject was calculated based on her own plasma Se concentration. The 24-h dietary record data for 3 consecutive days were collected to calculate their dietary intakes of protein together with each amino acid daily based on the China Food Composition Tables (CFCT). Ordinal polytomous logistic regression was applied to examine the determinants of BMI values for lactating women. For all subjects, the concentration of plasma SEPP1 and milk Se of participants with insufficient Se intake were significantly associated with the dietary intake of serine and 2 SAAs (methionine and cystine), respectively (P 0.05). No significant correlation was found between each amino acid related to the synthesis of endogenous serine and every biomarker of the Se nutrition status in subjects with an insufficient dietary protein intake (P 0.05). The ordinal logistic regression analysis showed that dietary protein intake (ordinal OR 1.012, 95% CI = 0.004-0.020, P = 0.002) and plasma SEPP1 (ordinal OR 0.988, 95% CI = - 0.023 to - 0.001, P = 0.036) affected the BMI value together in these lactating women. In conclusion, dietary serine and SAAs were found to directly affect the nutritional status, and both high protein intake and low plasma SEPP1 might be the health risks in these lactating Chinese women.

Methieillin-resistant Staphylococcus aureus (MRSA) can lead to pneumonia and septicemia with a rising incidence. As the first choice drug of MRSA, vancomycin causes more side effects and reduces sensitivity. Oxazolidinone antibiotics linezolid is confirmed to be used in the treatment of MRSA infection. This study compared the antibacterial activity and efficacy of linezolid and vancomycin on rat MRSA pneumonia model. SD rats were randomly separated into pneumonia group; vancomycin group and linezolid group. Survival rate was calculated and compared. PaO2 and pH were tested by blood gas analysis. Pulmonary wet/dry (W/D) ratio was determined. Serum TNF-α and IL-1β contents were detected by ELISA. Colony counting was performed by pulmonary tissue homogenate. Diameter of inhibition zone was measured. Minimum inhibition concentration (MIC) was evaluated by broth microdilution method. Both vancomycin and linezolid significantly improved survival rate, elevated PaO2 and pH, decreased W/D, and reduced TNF-α and IL-1β (P < 0.05). Bacterial inhibition diameter was 28±2 mm, colony counting was 22±6, and MIC was 1.2±0.3 μg/ml in linezolid group, which was obviously than that bacterial inhibition diameter at 21±3 mm, colony counting at 85±12, and MIC at 2.5±0.7 μg/ml in vancomycin group (P < 0.05). Both vancomycin and linezolid can treat MRSA pneumonia, inhibit inflammation, and improve survival rate. Linezolid exhibited stronger antibacterial action than vancomycin.

Radiotherapy is one of the most important clinical cancer treatments, which works mainly by delivering a prescribed radiation dose to the tumor tissues. However, high doses of radiation may also lead many irreversible damages to the surrounding normal tissues. Thereby, how to effectively reduce these side-effects has been a significant factor in influencing cancer therapeutic effect. In this work, we synthesized the hollow PtPd nanocubes with high-index facets, and investigated the radiation protection capability in vitro and in vivo. Our results showed the PtPd nanocrystals can decrease the ROS level and improve the survival rate of radiated cells. Meanwhile, survival rate of radiated mice can significantly increase from 0 to 30% after PtPd treatment. Consequently, the enzyme and ROS level in radiated mice can be recovered.

The heterogeneity in human breast cancer poses a challenge for effective treatment. Better understanding of tumor initiation and development will help to resolve this problem. Current models explaining intratumoral diversity include cancer stem cells, clonal evolution and cancer cell dedifferentiation and reprogramming. Herein, a new model, cancer transmission, is proposed to explain cancer heterogeneity. We found breast cancer cells (MCF10A.NeuT) were capable of transforming normal mammary epithelial cells (MCF10A). The transformed cells exhibited cancerous properties including enhanced proliferation and migration, loss of apical-basal polarity and depolarized acini structure associated with epithelial-mesenchymal transition (EMT). The transformed MCF10A cells displayed distinct EMT characteristics compared to parental cells. We further showed that cancer cell-secreted factors were sufficient to induce cancerous transformation of normal cells. Furthermore, transformed cells were resistant to radiation treatment, providing new insights into mechanisms underlying therapeutic resistance.

// Weihua Li 1, 2 , Huimin Bai 2 , Shiping Liu 3 , Dongyan Cao 1 , Hongying Wu 4 , Keng Shen 1 , Yanhong Tai 5, * and Jiaxin Yang 1, * 1 Department of Obstetrics and Gynecology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Wangfujing, Beijing 100730, China 2 Department of Obstetrics and Gynecology, Beijing Chao-Yang Hospital Affiliated to Capital Medical University, Beijing 100020, China 3 Departments of Obstetrics and Gynecology, Peking University First Hospital, Beijing 100034, China 4 Institute of Radiation Medicine, The Chinese Academy of Medical Sciences, Tianjin 300192, China 5 Department of Pathology, The Affiliated Hospital of Military Medical Science Academy of Chinese People’s Liberation Army (307 Hospital of Chinese People’s Liberation Army), Beijing 100071, China * These authors contributed equally to this work Correspondence to: Yanhong Tai, email: taiyanhong29@163.com Jiaxin Yang, email: yangjiaxin007@126.com Keywords: stearoyl-CoA desaturase; endometrial cancer; therapeutic target; cell growth; cell death Received: July 28, 2017 Accepted: December 26, 2017 Published: January 24, 2018 ABSTRACT Stearoyl-CoA desaturase 1 (SCD1) is an established molecular target in many primary tumors including breast, lung, pancreatic, colon and hepatocellular carcinomas. However, its potential role in supporting endometrial cancer growth and progression has not yet been determined. In this study, we evaluated the value of SCD1 as a candidate therapeutic target in human endometrial cancer. Compared with secretory and post-menopausal endometrium, SCD1 was highly expressed in normal endometrium of proliferative phase, endometrial hyperplasia and endometrial carcinoma, while was absent or low expression in non-malignant control stromal cells and adjacent normal endometrium. Knockdown of SCD1 significantly repressed endometrial cancer cell growth and induced cell apoptosis. Both short hairpin RNA targeted knockdown and chemical inhibitor of SCD1 suppressed the foci formation of AN3CA, a metastatic endometrial cell line. Xenograft model further demonstrated that reduced SCD1 expression impaired endometrial cancer growth in vivo . Taken together, these findings indicate that SCD1 is a potentially therapeutic target in human endometrial cancer. Inhibiting lipid metabolism in cancer cells would be a promising strategy for anti-cancer therapy.

Background We examined the influence of pre-pregnancy body weight on the rates of attempted and successfully assisted-vaginal delivery. Methods We used 2008–2016 inpatient records including 3408 women who had singleton gestations and needed operative delivery assistance to conduct a retrospective cohort study. Patients were categorized based on pre-pregnancy BMI (normal weight = 18.5 to less than 25 or obese = 30 or greater). We used logistic regression to estimate odds ratios and 95% confidence intervals of attempted and successful forceps or vacuum-assisted vaginal delivery by body weight adjusted for marital status, age, gestational age, induction of labor, episiotomy, diabetes, and birth weight. Results The proportion of women with attempted either vacuum or forceps was lower among women who were obese pre-pregnancy compared to women who were normal weight. Women with excessive gestational weight gain, large for gestational age neonates, and diabetes were less likely to have a vacuum-assisted or forceps-assisted vaginal delivery attempted. Conversely, women who received labor augmentation or induction, used epidural anesthesia, gained inadequate weight, and delivered a small for gestational age infant were more likely to have a vacuum-assisted or forceps-assisted vaginal delivery attempted. Compared to normal weight women, obese women who received forceps-assisted vaginal delivery were more likely to have a successful vaginal delivery. Conclusion Women who had normal weight had higher likelihood to attempt assisted vaginal delivery compared to women who had pre-pregnancy obesity. However, when assisted vaginal delivery was attempted, success rates were higher when forceps-assisted delivery was used compared to vacuum-assisted delivery.

Hematopoietic injury is the most common side effect of radiotherapy. However, the methods available for the mitigating of radiation injury remain limited. Xuebijing injection (XBJ) is a traditional Chinese medicine used to treat sepsis in the clinic. In this study, we investigated the effects of XBJ on the survival rate in mice with hematopoietic injury induced by γ ray ionizing radiation (IR). Mice were intraperitoneally injected with XBJ daily for seven days after total body irradiation (TBI). Our results showed that XBJ (0.4 mL/kg) significantly increased 30-day survival rates in mice exposed to 7.5 Gy TBI. This effect may be attributable to improved preservation of white blood cells (WBCs) and hematopoietic cells, given that bone marrow (BM) cells from XBJ-treated mice produced more granulocyte-macrophage colony forming units (CFU-GM) than that in the 2 Gy/TBI group. XBJ also decreased the levels of reactive oxygen species (ROS) by increasing glutathione (GSH) and superoxide dismutase (SOD) levels in serum and attenuated the increased BM cell apoptosis caused by 2 Gy/TBI. In conclusion, these findings suggest that XBJ enhances the survival rate of irradiated mice and attenuates the effects of radiation on hematopoietic injury by decreasing ROS production in BM cells, indicating that XBJ may be a promising therapeutic candidate for reducing hematopoietic radiation injury.

The aim of this study was to evaluate the effect and underlying mechanism of Yangyinqingfei decoction on radiation-induced lung injury in rats. Wistar rats (n=75) were randomly divided into five experimental groups (A-E). Rats in two of the groups were administered saline solution, whereas rats in the remaining three groups were administered different doses of Yangyinqingfei decoction. After one week, the rats were irradiated with a single dose of 25 Gy to their right hemi-thoraxes by a 60Co γ-ray, with the exception of the control group, which underwent sham irradiation. The effect of Yangyinqingfei decoction was assessed one, two and four weeks post-irradiation according to the pathological changes and the right lung index (wet weight of right lung/body weight ×100%). Expression levels of matrix metalloproteinase-12 (MMP-12) and tissue inhibitors of metalloproteinases-1 (TIMP-1) in lung tissue were determined using the reverse transcription-polymerase chain reaction and western blot analysis. Pretreatment with Yangyinqingfei resulted in a significant dose-dependent resistance to radiation-induced body weight loss. The expression of MMP-12 and TIMP-1 increased following irradiation. However, the levels of MMP-12 and TIMP-1 in groups receiving Yangyinqingfei were lower four weeks after irradiation compared with those in rats administered saline. Cumulatively, these results suggest that Yangyinqingfei has a protective effect on radiation-induced lung injury in rats, possibly by downregulating MMP-12 and TIMP-1 expression.

Our recent studies showed that total body irradiation (TBI) induces long-term bone marrow (BM) suppression in part by induction of hematopoietic stem cell (HSC) senescence through NADPH oxidase 4 (NOX4)-derived reactive oxygen species (ROS). Therefore, in the present study we examined if resveratrol (3,5,4’-trihydroxy-trans-stilbene), a potent antioxidant and a putative activator of Sirtuin 1 (Sirt1), can ameliorate TBI-induced long-term BM injury by inhibiting radiation-induced chronic oxidative stress and senescence in HSCs. Our results showed that pretreatment with resveratrol not only protected mice from TBI-induced acute BM syndrome and lethality but also ameliorated TBI-induced long-term BM injury. This later effect is likely attributed to resveratrol-mediated reduction of chronic oxidative stress in HSCs, because resveratrol treatment significantly inhibited TBI-induced increase in ROS production in HSCs and prevented mouse BM HSCs from TBI-induced senescence, leading to a significant improvement of HSC clonogenic function and long-term engraftment after transplantation. The inhibition of TBI-induced ROS production in HSCs is likely attributable to resveratrol-mediated down-regulation of NOX4 expression and up-regulation of Sirt1, superoxide dismutase 2 (SOD2), and glutathione peroxidase 1 (GPX1) expression. Furthermore, we showed that resveratrol increased Sirt1 deacetylase activity in BM hematopoietic cells; and Ex527, a potent Sirt1 inhibitor, can attenuate resveratrol-induced SOD2 expression and the radioprotective effect of resveratrol on HSCs. These findings demonstrate that resveratrol can protect HSCs from radiation at least in part via activation of Sirt1. Therefore, resveratrol has the potential to be used as an effective therapeutic agent to ameliorate TBI-induced long-term BM injury.

MicroRNAs are short regulatory RNAs that negatively modulate gene expression at the posttranscriptional level and are deeply involved in the pathogenesis of several types of cancer. The miRNA-130a has been shown to play a role in antagonizing the inhibitory effects of GAX on endothelial cell proliferation, migration and tube formation, and antagonizing the inhibitory effects of HoxA5 on tube formation in vitro. Here the authors show, for the first time, that miRNA-130a expression is increased in nonsmall cell lung cancer (NSCLC) tissues. Statistical analysis showed that overexpression of miRNA-130a was strongly associated with lymph node metastasis, stage of tumor node metastasis classification and poor prognosis. Moreover, there was a significant difference in miRNA-130a expression levels between smoking and nonsmoking patients. Multivariate Cox regression analysis showed that miRNA-130a was an independent prognostic factor for patients with NSCLC. Together, these data suggest that miRNA-130a may comprise a potential novel prognostic marker for this disease.

miRNA-22 was previously reported to be a tumor suppressor. The aim of this study was to explore the expression and function of miRNA-22 in esophageal squamous cell carcinoma (ESCC). Expression of miRNA-22 in 100 ESCC tissues was examined by q-PCR. The correlation between miRNA-22 level and clinicopathological features was analyzed using SPSS16.0 statistical software. Moreover, the effect of miRNA-22 expression on radiosensitivity of ESCC cells was examined. miRNA-22 expression decreased in ESCC tissues, and statistical analyses showed that the expression of miRNA-22 was associated with the stage of clinical classification. No correlation was found between miRNA-22 expression and the overall survival of ESCC patients. However, significant positive correlation was found between miRNA-22 expression and the survival of patients who received radiotherapy (P < 0.05). Increased expression of miRNA-22 sensitized ESCC cells to γ-ray radiation and promoted the apoptosis of ESCC cells induced by γ-ray radiation. Increased expression level of miRNA-22 had effects on Rad51 expression after irradiation. These results demonstrate for the first time that decreased miRNA-22 expression correlates with increased radiotherapy resistance of ESCC, and that this effect is mediated, at least in part, by the Rad51 pathway.

Cks1/Overexpression/Prognosis/Radiation resistance/ESCC. Purposes The Cks1 protein is a member of the highly conserved family of Cks/Suc1 proteins, which interact with Cdks, and was found to be an essential cofactor for efficient Skp2-dependent ubiquitination of p27. The present study was undertaken to examine the expression status of Cks1 in esophageal squamous cell carcinoma and its significance. M aterials and Methods The expression of Cks1 in 140 esophageal squamous cell carcinoma patients was examined by immunohistochemistry. The correlations between C ks1 expression and tumor clinicopathologic features were analyzed. The effects of Cks1 expression on radiotherapy results were also examined. Res ults In the present study, we found that Cks1 is overexpressed in esophageal squamous cell carcinoma tissues. Elevated expression of Cks1 correlates significantly with tumor stage and positive lymph node metastasis (p < 0.05). Moreover, a significant negative correlation was found between Cks1 expression and the survival of patients who received r adiotherapy (p < 0.05). At the molecular level, forced expression of Cks1 promotes the radio-resistance ability of EC9706 cells. Knockdown of Cks1 expression sensitizes cancer cells to radiation, and a wobble mutant of Cks1 that is resistant to Cks1 siRNA can rescue this effect. Conclusions These results demonstrate for the first time that overexpression of Cks1 correlates with the increased radiotherapy resistance of esophageal squamous cell carcinoma.

p38 mitogen-activated protein kinases (p38) has been shown to be activated in hematopoietic stem and progenitors cells after exposure to ionizing radiation (IR) and its activation has been implicated in bone marrow (BM) suppression under various pathological conditions. Therefore, in the present study we investigated whether inhibition of p38 activity alone with SB203580 (SB, a specific p38 inhibitor) or in combination with granulocyte colony-stimulating factor (G-CSF) can mitigate total body irradiation (TBI)-induced BM damage and lethality. Our results showed that p38 inhibition with SB had no significant effect on the 30-day survival rates of the mice exposed to 7.2 Gy TBI when it was used alone but increased the survival of the mice when it was combined with G-CSF. This combined effect may be attributable to a better preservation or stimulation of hematopoietic stem and progenitor cells, because BM cells from SB and G-CSF-treated mice produced more colony forming units-granulocyte-macrophage (CFU-GM) and 4-week cobblestone area forming cells (CAFCs) than the cells from either SB or G-CSF-treated mice after TBI in a colony forming cell assay and a CAFC assay, respectively. These findings suggest that the combined therapy with SB and G-GSF is more effective in mitigating TBI-induced acute BM injury than either agent alone.

Xiao-Dong Zhang*, Hong-Ying Wu*, Di Wu, Yue-Ying Wang, Jian-Hui Chang, Zhi-Bin Zhai, Ai-Min Meng, Pei-Xun Liu, Liang-An Zhang, Fei-Yue FanInstitute of Radiation Medicine, Chinese Academy of Medical Sciences and Peking Union Medical College, and Tianjin Key Laboratory of Molecular Nuclear Medicine, Tianjin, People’s Republic of China *The authors contributed equally to this workAbstract: Gold nanoparticles have potential applications in biomedicine, but one of the important concerns is about their safety. Most toxicology data are derived from in vitro studies and may not reflect in vivo responses. Here, an animal toxicity study of 13.5 nm gold nanoparticles in mice is presented. Animal survival, weight, hematology, morphology, and organ index are characterized at different concentrations (137.5–2200 µg/kg) over 14–28 days. The results show that low concentrations of gold nanoparticles do not cause an obvious decrease in body weight or appreciable toxicity, even after their breakdown in vivo. High concentrations of gold nanoparticles induced decreases in body weight, red blood cells, and hematocrit. It was also found that gold nanoparticles administered orally caused significant decreases in body weight, spleen index, and red blood cells. Of the three administration routes, the oral and intraperitoneal routes showed the highest toxicity, and the tail vein injection showed the lowest toxicity. Combining the results of all of these studies, we suggest that targeted gold nanopartices by tail vein injection may be suitable for enhancement of radiotherapy, photothermal therapy, and related medical diagnostic procedures.Keywords: gold nanoparticles, in vivo, toxicity