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Bojsen Kyed posted an update 5 days, 8 hours ago
In 2019, the International Agency for Research on Cancer (IARC) “Preamble to the IARC Monographs” expanded guidance regarding the scientific approaches that should be employed in its monographs. These amendments to the monograph development process are an improvement but still fall short in several areas. While the revised Preamble lays out broad methods and approaches to evaluate scientific evidence, there is a lack of specificity with regard to how IARC Working Groups will conduct consistent evaluations in a standardized, objective, and transparent manner; document systematic review and evidence integration actions, and substantiate how these actions and decisions inform the ultimate classifications. Furthermore, no guidance is provided to ensure Working Groups consistently incorporate mechanistic evidence in a robust manner using a defined approach in the context of 21st century knowledge of modes of action. Nor are the conclusions of the working groups subjected to outside, independent scientific peer review. Continued improvements and modernization of the procedures for evaluating, presenting, and communicating study quality, and in the methods used to conduct and peer-review evidence-based decision making will benefit the Working Group members, the IARC Monographs Programme overall, and the international regulatory community and public who rely upon the monographs. BACKGROUND Early spontaneous preterm delivery is often associated with microbial invasion of the amniotic cavity and/or intra-amniotic inflammation. OBJECTIVE To develop and validate clinically feasible multivariable prediction models of spontaneous delivery within 7 days and microbial invasion of the amniotic cavity in women admitted with diagnose of preterm labor and intact membranes below 34 weeks. STUDY DESIGN We used data from a cohort of women admitted from 2012 to 2018 with diagnosis of preterm labor below 34 weeks who had undergone amniocentesis to rule out microbial invasion of the amniotic cavity. Main outcome was spontaneous delivery within 7 days from admission. Secondary outcome was microbial invasion of the amniotic cavity, defined by a positive culture and/or 16S ribosomal RNA gene in amniotic fluid. The sample (n= 358) was divided into derivation (2012-2016) and validation cohorts (2017-2018). Logistic regression models using a stepwise selection of variables were developed for the outcomes evwithin 7 days of 87% , a false-positive rate of 33%, negative predictive value of 80% and negative Likelihood ratio of 0.1908. For microbial invasion of the amniotic cavity, two independent predictors of the amniotic cavity were identified amniotic fluid glucose and maternal CRP. The AUROC in the validation cohort was 0.83 (95% confidence interval (CI) 0.70-0.96) with a detection rate of 76%, a false positive rate of 8%, negative predictive value of 93% and negative Likelihood ratio of 0.2591. CONCLUSIONS In women with preterm labor, we propose two clinically feasible prediction models to classify as low versus high-risk of spontaneous delivery within 7 days and of microbial invasion of the amniotic cavity. The models showed a high diagnostic performance and could be of value to optimize clinical management. Recent studies have shown that complement C1q tumor necrosis factor related proteins (CTRPs) such as adiponectin, have different regulatory roles on the cardiovascular system. CTRP2 is the most similar to adiponectin and one of the best characterized beneficial adipokines important in the regulation of whole body metabolism. However, there were no studies about the relationship between CTRP2 and Coronary artery disease (CAD). This study aimed to evaluate the serum CTRP2 levels in patient with Coronary artery disease. In this study, a total of 82 participants who underwent vascular angiography were included. All of subjects were male. According to their coronary angiography results, all participants were divided into CAD group (n = 42) and control group (n = 40). Serum CTRP2 levels were determined quantitatively with enzyme-linked immunosorbent assay (ELISA). Our study for the first time showed that the CTRP2 levels were higher in CAD patients (1.79 ± 1.46 ng/mL) compared to control subjects (1.08 ± 0.78 ng/mL; p = 0.001). selleck compound The levels of CTRP2 also were positively correlated with severity of CAD (r = 0.356, p = 0.001). In addition, logistic regression analysis indicated that CTRP2 had an independent association with the risk of CAD (OR [CI] = 3.366 [1.605-7.060]; p = 0.001). Increased levels of CTRP2 in CAD patients were independently associated with the progression of the CAD, it might be regarded as a novel biomarker for assessing the risk of CAD; however, more study is required in this regard. BACKGROUND Investigation into the anti-cancer activities of natural products and their derivatives represents an efficient approach to develop safe and effective chemotherapeutic agents for the treatment of colorectal cancer. Helveticoside is a biologically active component of the seed extract of Descurainia sophia. This compound has been reported to regulate the genes related to cell proliferation and apoptosis in lung cancer cells, however its anticancer activity has not been fully explored yet. METHODS Cell viability was evaluated by MTT and Trypan blue exclusion assay; cell apoptosis was measured by flow cytometry; mitochondrial membrane potential was determined by using JC1-mitochondrial membrane potential assay kit; protein levels were determined by western blot assay; in vivo tumor growth was assessed in a xenograft nude mice model. RESULTS The current study demonstrated the in vitro anti-cancer activity of helveticoside against colorectal cancer using colorectal cancer cells SW480 and HCT116. Moreover, induction of apoptosis was found to mediate the cytotoxic action of helveticoside on SW480 and HCT116 cells. Based on the decrease in the mitochondrial membrane potential, upregulation of Bax, downregulation of Bcl-2 and cleavage of caspase-3 and 9, apoptosis was induced by helveticoside via mitochondria-mediated intrinsic apoptotic signaling pathways in colorectal cancer cells. Besides, using p53-knockout SW480 cells, the cytotoxic action of helveticoside was found to be p53-dependent. More importantly, administration of helveticoside inhibited the growth of HCT116 cells derived-colorectal cancer xenograft in mice via activation of apoptosis. CONCLUSIONS Helveticoside might be a potential candidate for the development of novel chemotherapeutic agents for the treatment of colorectal cancer, while the potential toxic effects of helveticoside may be worthy of further investigations.