IRE1 signaling is essential for ischemia-induced vascular endothelial growth factor-A expression and contributes to angiogenesis and tumor growth in vivo

In solid tumors, cancer cells subjected to ischemic conditions trigger distinct signaling pathways contributing to angiogenic stimulation and tumor development. Characteristic features of tumor ischemia include hypoxia and glucose deprivation, leading to the activation of hypoxia-inducible factor-1-dependent signaling pathways and to complex signaling events known as the unfolded protein response. Here, we show that the activation of the endoplasmic reticulum stress sensor IRE1 is a common determinant linking hypoxia- and hypoglycemia-dependent responses to the up-regulation of vascular endothelial growth factor-A (VEGF-A). Tumor cells expressing a dominant-negative IRE1 transgene as well as Ire1alpha-null mouse embryonic fibroblasts were unable to trigger VEGF-A up-regulation upon either oxygen or glucose deprivation. These data correlated with a reduction of tumor angiogenesis and growth in vivo. Our results therefore suggest an essential role for IRE1-dependent signaling pathways in response to ischemia and identify this protein as a potential therapeutic target to control both the angiogenic switch and tumor development.     

离子对反相高效液相色谱法测定小柴胡胶囊制剂中黄芩苷的含量

目的：研究了离子对－反相高效液相色谱法测定小柴胡胶囊制剂中黄芩苷的含量。方法：用５０％甲醇作溶剂、超声波振荡法提取样品。色谱条件用μ－ＢｏｎｄｐａｋＣ１８作分析柱,ＷａｔｅｒｓＧｕａｒｄ－ＰＡＫＣ１８作保护柱,水相（取庚烷碘酸钠０．４０ｇ,磷酸二氢钠３．９０ｇ冰醛酸２０ｍｌ,加水溶解并稀释至１０００ｍｌ）＝甲醇（５６：４４）作流动相,流速１ｍｌ／ｍｉｎ,ＵＶ检测波长为２７５ｎｍ。结果：黄芩苷与 份     

Proteomic approaches to tumor marker discovery

CONTEXT: Current tumor markers for ovarian cancer still lack adequate sensitivity and specificity to be applicable in large populations. High-throughput proteomic profiling and bioinformatics tools allow for the rapid screening of a large number of potential biomarkers in serum, plasma, or other body fluids. OBJECTIVE: To determine whether protein profiles of plasma can be used to identify potential biomarkers that improve the detection of ovarian cancer. DESIGN: We analyzed plasma samples that had been collected between 1998 and 2001 from patients with sporadic ovarian serous neoplasms before tumor resection at various International Federation of Gynecology and Obstetrics stages (stage I [n = 11], stage II [n = 3], and stage III [n = 29]) and from women without known neoplastic disease (n = 38) using proteomic profiling and bioinformatics. We compared results between the patients with and without cancer and evaluated their discriminatory performance against that of the cancer antigen 125 (CA125) tumor marker. RESULTS: We selected 7 biomarkers based on their collective contribution to the separation of the 2 patient groups. Among them, we further purified and subsequently identified 3 biomarkers. Individually, the biomarkers did not perform better than CA125. However, a combination of 4 of the biomarkers significantly improved performance (P < or =.001). The new biomarkers were complementary to CA125. At a fixed specificity of 94%, an index combining 2 of the biomarkers and CA125 achieves a sensitivity of 94% (95% confidence interval, 85%-100.0%) in contrast to a sensitivity of 81% (95% confidence interval, 68%-95%) for CA125 alone. CONCLUSIONS: The combined use of bioinformatics tools and proteomic profiling provides an effective approach to screen for potential tumor markers. Comparison of plasma profiles from patients with and without known ovarian cancer uncovered a panel of potential biomarkers for detection of ovarian cancer with discriminatory power complementary to that of CA125. Additional studies are required to further validate these biomarkers.     

Long Hemodialysis Duration Predicts Delayed Graft Function in Renal Transplant Recipients From Living Donor: A Single-Center Study

BackgroundThis study aims to determine the ratio of delayed graft function in renal transplant recipients from living donors and the predictive value of hemodialysis time before transplant for delayed graft function.MethodsWe conducted a study on 116 adult patients who were diagnosed with end-stage kidney disease and were treated with hemodialysis and transplanted kidneys from living donors for 2 years (from June 2018 to June 2020). Delayed graft function event was collected for each patient.ResultsThe recipients had a median age of 36.5 years old, in which 55.2% of them were men, 4.3% of them had the diabetic mellitus, and the median hemodialysis duration was 6 months. The ratio of positive panel-reactive antibody was 33.6% and vascular reconstruction of the donor's kidney was 16.4%. The ratio of delayed graft function was 12.2% (14 of 116 patients). Delayed graft function significantly related to positive panel-reactive antibody, long duration of hemodialysis before transplant, and vascular reconstruction of donor's kidney with P < .001. Duration of hemodialysis before kidney transplant had a predictive value for delayed graft function (area under the curve, 0.83; P < .001).ConclusionDelayed graft function was not rare in renal transplant recipients from living donors. Duration of hemodialysis before kidney transplant was a good predictor for delayed graft function.     

Methylene blue adsorption mechanism of activated carbon synthesised from cashew nut shells

Activated carbon produced from agricultural products and wastes has been applied widely to remove pollutants in the field of waste water treatment. However, the cost of this adsorbent depends so much on the raw material sources. Therefore, the approach of producing activated carbon from agricultural waste is strongly recommended due to economic advantages and environmental protection. One of the potential feed-stocks for the activated carbon production is cashew nut shell (CNS) waste which could reduce the negative impacts to the environment from the cashew nut processing industry and simultaneously enhance the values of the related products. This study focused on evaluating the influences of variable factors, such as activation temperature and time, on the properties of the activated carbon obtained from CNS. Methylene blue (MB) adsorption was applied to understand the adsorption mechanism of the products. The results show that increasing the activation temperature led to a rise in the adsorption capacity of the activated carbon within the temperature range of 800 to 850 °C. Otherwise, the values were reduced when the temperature was greater than 850 °C and this was related to the thermal decomposition of carbon. The adsorption capacity also increased when the activation time was changed from 30 min to 50 min. However, in the activation time range from 50 to 70 min, there was a reduction of the adsorption capacity of CNS-based activated carbon. The results also show that the MB adsorption of the activated carbon occurred with one-site-occupancy in the first layer and then layer-by-layer adsorption formation.

Activated carbon produced from agricultural products and wastes has been applied widely to remove pollutants in the field of waste water treatment.     

The impact of alcohol consumption and physical activity on breast cancer: The role of breast cancer risk

High alcohol consumption and physical inactivity are known breast cancer risk factors. However, whether the association between these lifestyle factors and breast cancer is modified by a woman's additional breast cancer risk factors has never been studied. Therefore, a population-based prospective cohort study of 57,654 Swedish women aged 40–74 years, including 957 breast cancer cases, was performed. Alcohol consumption and physical activity were measured with validated web-based self-report questionnaires. The Tyrer–Cuzick risk prediction model was used to determine a woman's 10-year risk of developing breast cancer. Logistic regression models were used to explore whether the effect of alcohol consumption and physical activity on breast cancer was modified by additional breast cancer risk factors. Findings showed that increased alcohol consumption was associated with a higher breast cancer risk (OR = 1.26, 95% CI 1.01, 1.59). However, the association between lifestyle factors (alcohol consumption and physical activity) and breast cancer was generally the same for women at below average, average and above average risk of developing breast cancer. Therefore, additional breast cancer risk factors do not appear to modify the association between lifestyle (alcohol consumption and physical activity) and breast cancer. Considering the general health benefits, preventative lifestyle recommendations can be formulated about alcohol consumption and physical activity for women at all levels of breast cancer risk.