The human Nox4: gene,structure, physiological function and pathological significance

Increased generation of reactive oxygen species (ROS) has been implicated in the pathogenesis of a variety of diseases such as cardiovascular diseases and cancer. NADPH oxidase (Nox), a multicomponent enzyme, has been identified as one of the key sources of ROS. Nox4, one of the seven members of Nox family (Nox1, Nox2, Nox3, Nox4, Nox5, Duox1 and Duox2), has been extensively investigated in recent years. Its unique structures result in the constitutive generation of hydrogen peroxide (H₂O₂) as the main product. As a key oxygen sensor, Nox4-derived H₂O₂ plays diverse roles in cell proliferation, migration and death. Increased expression of Nox4 in cancer has been observed, which participates in metastasis, angiogenesis and apoptosis. Expression of Nox4 in endothelial cells actively mediated endothelial activation, dysfunction and injury, which contributes to the development of atherosclerosis, hypertension, cardiac hypertrophy and among others. This article explores the experimental studies related to the gene, structure, physiological function and pathological significance of Nox4. As Nox4 might serve as a potential target for the therapy of cardiovascular diseases and cancer, the Nox4 inhibitor is also discussed in this article.     

Elastin-like polypeptides and their applications in anticancer drug delivery systems: a review

Abstract

Elastin-like polypeptides (ELPs) are large molecular weight biopolymers. They have been widely studied as macromolecular carriers for targeted delivery of drugs. The aim of the present article is to review the available information on ELPs (including our recent investigations), their properties, drug delivery applications to tumor sites and future perspectives. This review also provides information on the use of short synthetic ELPs for making ELP-drug conjugates, for targeted delivery of anticancer drugs. In the present review we also focus on the point that short ELPs can also be used for targeting anticancer drugs to tumor sites as they behave similar to long ELPs regarding their capacity to undergo inverse temperature transition (ITT) behavior.     

m6A regulators are associated with osteosarcoma metastasis and have prognostic significance: A study based on public databases

Background:Osteosarcoma represents the most common malignant bone tumor with high metastatic potential and inferior prognosis. RNA methylation (N6-methyladenosine [m6A]) is a prevalent RNA modification that epigenetically influences numerous biological processes including tumorigenesis. This study aims to determine that m6A regulators are significant biomarkers for osteosarcoma, and establish a prognostic model to predict the survival of patients.Methods:In this study, we comprehensively analyzed the underlying associations between m6A regulators’ mRNA expressions and metastasis as well as prognosis of osteosarcoma patients in the Cancer Genome Atlas. Multivariate Cox-regression analysis was used to screen regulators that were significantly associated with overall survival of osteosarcoma patients. Least absolute shrinkage and selection operator (LASSO) Cox-regression analysis was used for constructing m6A regulator-based osteosarcoma prognostic signature.Results:Some of the regulators exhibited aberrant mRNA levels between osteosarcoma samples with and without metastasis. Multivariate Cox-regression analysis identified several regulators with potential prognostic significance. A risk score formula consisted of methyltransferase-like 3, YTH domains of Homo sapiens, and fat mass and obesity-associated protein was obtained through which patients could be prognostically stratified independently of potential confounding factors. The signature was also significantly associated with the metastatic potential of osteosarcoma. All the analyses could be well reproduced in another independent osteosarcoma cohort from the Gene Expression Omnibus.Conclusions:In conclusion, this study first revealed potential roles of m6A regulators in osteosarcoma metastasis and prognosis, which should be helpful for its clinical decision-making.     

Chlorinated pesticide residues in human breast milk collected from southern Jordan in 2012/2013

Chlorinated pesticide residues in human breast milk from five southern Jordan districts were analyzed in 2012/2013. The total number of samples from all districts was 100. The number of samples gathered from each district was collected according to their population densities. The present study shows that 59% of the samples which contained pesticides’ residues were p,p’-DDE, 30% contained β-HCH, 10% contained p,p′-DDT, 6% contained α-HCH, 2% contained heptachlor and 1% contained endrin. These human milk samples were free of aldrin, dieldrin, α-endosulfan, β-endosulfan, HCB, γ-HCH, o,p′-DDD, o,p′-DDT and o,p′-DDE. The levels of the six mentioned compounds detected in all mother’s milk samples were higher in Ghor El-Safi district compared with the other four districts. In this study, it is recommended to continue the pesticides residues monitoring in all parts of Jordan, particularly in Ghor El-Safi district and other regions in the cultivated Jordan Valley.     

Cancer patients with acute coronary syndrome have non-superior bleeding risk compared to patients with similar characteristics – a propensity score analysis from the ProACS registry

IntroductionThe management of acute coronary syndrome (ACS) in malignancy is challenging due to higher bleeding risk.MethodsWe analyzed patients with cancer (active or in the previous five years) prospectively included in the ProACS registry between 2010 and 2019. Our aim was to assess safety (major bleeding, primary endpoint) and secondary efficacy endpoints (in-hospital mortality and combined in-hospital mortality, reinfarction and ischemic stroke) of ACS treatment. Propensity score matching analysis (1:1) was further performed to better understand predictors of outcomes.ResultsWe found 934 (5%) cancer patients out of a total of 18 845 patients with ACS. Cancer patients had more events: major bleeding (2.9% vs. 1.5%), in-hospital mortality (5.8% vs. 3.4%) and the combined endpoint (7.4% vs. 4.9%). The primary endpoint was related to cancer diagnosis (OR 1.97), previous bleeding (OR 7.09), hemoglobin level (OR 4.94), atrial fibrillation (OR 3.50), oral anticoagulation (OR 3.67) and renal dysfunction. Mortality and the combined secondary endpoint were associated with lower use of invasive coronary angiography and antiplatelet and neurohormonal blocker therapy. After propensity score matching (350 patients), there were no statistically significant differences in endpoints between the populations.ConclusionBleeding risk was not significant higher in the cancer population compared to patients with similar characteristics, nor were mortality or ischemic risk. The presence of cancer should not preclude simultaneous ACS treatment.     

Breast Density Analysis Using an Automatic Density Segmentation Algorithm

Breast density is a strong risk factor for breast cancer. In this paper, we present an automated approach for breast density segmentation in mammographic images based on a supervised pixel-based classification and using textural and morphological features. The objective of the paper is not only to show the feasibility of an automatic algorithm for breast density segmentation but also to prove its potential application to the study of breast density evolution in longitudinal studies. The database used here contains three complete screening examinations, acquired 2 years apart, of 130 different patients. The approach was validated by comparing manual expert annotations with automatically obtained estimations. Transversal analysis of the breast density analysis of craniocaudal (CC) and mediolateral oblique (MLO) views of both breasts acquired in the same study showed a correlation coefficient of ρ = 0.96 between the mammographic density percentage for left and right breasts, whereas a comparison of both mammographic views showed a correlation of ρ = 0.95. A longitudinal study of breast density confirmed the trend that dense tissue percentage decreases over time, although we noticed that the decrease in the ratio depends on the initial amount of breast density.     

Evidence-based Clinical Practice Guidelines for Interventional Pain Management in Cancer Pain

Intractable cancer pain not amenable to standard oral or parenteral analgesics is a horrifying truth in 10–15% of patients. Interventional pain management techniques are an indispensable arsenal in pain physician''s armamentarium for severe, intractable pain and can be broadly classified into neuroablative and neuromodulation techniques. An array of neurolytic techniques (chemical, thermal, or surgical) can be employed for ablation of individual nerve fibers, plexuses, or intrathecalneurolysis in patients with resistant pain and short life-expectancy. Neuraxial administration of drugs and spinal cord stimulation to modulate or alter the pain perception constitutes the most frequently employed neuromodulation techniques. Lately, there is a rising call for early introduction of interventional techniques in carefully selected patients simultaneously or even before starting strong opioids. After decades of empirical use, it is the need of the hour to head towards professionalism and standardization in order to secure credibility of specialization and those practicing it. Even though the interventional management has found a definite place in cancer pain, there is a dearth of evidence-based practice guidelines for interventional therapies in cancer pain. This may be because of paucity of good quality randomized controlled trials (RCTs) evaluating their safety and efficacy in cancer pain. Laying standardized guidelines based on existing and emerging evidence will act as a foundation step towards strengthening, credentialing, and dissemination of the specialty of interventional cancer pain management. This will also ensure an improved decision-making and quality of life (QoL) of the suffering patients.     

血清人附睾分泌蛋白4在卵巢上皮性癌中的临床价值

目的 研究血清人附睾蛋白4(HE4)在卵巢恶性肿瘤中的诊断价值.方法 用酶联疫吸附试验方法对卵巢上皮性癌组(54例)、盆腔良性疾病组(60例)、正常组(60例)妇女血清中HE4和CA125进行双盲检测,结果以中位数表示,分析比较两者单独检测诊断卵巢恶性肿瘤的价值.血清HE4和CA125的正常值分别为0～ 140pmol/L和0～ 35KU/L,其中任一指标高于正常即为阳性.结果 ①卵巢上皮性癌组血清HE4和CA125水平分别为142.72pmol/L和136.07KU/L,分别与盆腔良性疾病组(分别为63.72pmol/L和72.20KU/L)和正常组(分别为57.82pmol/L和57.42KU/L)比较,差异均有统计学意义(P＜0.01).②以盆腔良性疾病组作参照人群时,HE4和CA125单独检测的受试者工作特征曲线下面积(ROC-AUC)分别为0.958和0.886,两者比较,差异有统计学意义(P＜0.001).③以ROC曲线最左上方的点130 pmol/L、正常组95％参考值80pmol/L和正常值的上限140pmol/L为界值点,比较HE4单项检测对卵巢上皮性恶性肿瘤的诊断能力,结果显示,界值点为80pmol/L的特异度和阳性预测值均为88％,明显低于界值点为130(分别为93％和90％)和140pmol/L(分别为93％和95％)时的特异度和阳性预测值(P＜0.01).结论 HE4单项检测诊断卵巢上皮性恶性肿瘤的特异度优于CA125单项检测.以140pmol/L为界值点,对卵巢上皮性恶性肿瘤的早期诊断准确率更高,而以130pmol/L为界值点有利于卵巢上皮性恶性肿瘤的筛查、降低漏诊率.