DNA Aptamers as Molecular Probes for Colorectal Cancer Study

Understanding the molecular features of specific tumors can increase our knowledge about the mechanism(s) underlying disease development and progression. This is particularly significant for colorectal cancer, which is a heterogeneous complex of diseases developed in a sequential manner through a multistep carcinogenic process. As such, it is likely that tumors with similar characteristics might originate in the same manner and have a similar molecular behavior. Therefore, specific mapping of the molecular features can be potentially useful for both tumor classification and the development of appropriate therapeutic regimens. However, this can only be accomplished by developing high-affinity molecular probes with the ability to recognize specific markers associated with different tumors. Aptamers can most easily meet this challenge based on their target diversity, flexible manipulation and ease of development.Using a method known as cell-based Systematic Evolution of Ligands by Exponential enrichment (cell-SELEX) and colorectal cancer cultured cell lines DLD-1 and HCT 116, we selected a panel of target-specific aptamers. Binding studies by flow cytometry and confocal microscopy showed that these aptamers have high affinity and selectivity. Our data further show that these aptamers neither recognize normal colon cells (cultured and fresh), nor do they recognize most other cancer cell lines tested.The selected aptamers can identify specific biomarkers associated with colorectal cancers. We believe that these probes could be further developed for early disease detection, as well as prognostic markers, of colorectal cancers

Molecular characterization of the CRa gene conferring clubroot resistance in Brassica rapa

Clubroot disease is one of the major diseases affecting Brassicaceae crops, and a number of these crops grown commercially, such as Chinese cabbage (Brassica rapa L. ssp. pekinensis), are known to be highly susceptible to clubroot disease. To provide protection from this disease, plant breeders have introduced genes for resistance to clubroot from the European turnip into susceptible lines. The CRa gene confers specific resistance to the clubroot pathogen Plasmodiophora brassicae isolate M85. Fine mapping of the CRa locus using synteny to the Arabidopsis thaliana genome and partial genome sequences of B. rapa revealed a candidate gene encoding a TIR-NBS-LRR protein. Several structural differences in this candidate gene were found between susceptible and resistant lines, and CRa expression was observed only in the resistant line. Four mutant lines lacking clubroot resistance were obtained by the UV irradiation of pollen from a resistant line, and all of these mutant lines carried independent mutations in the candidate TIR-NBS-LRR gene. This genetic and molecular evidence strongly suggests that the identified gene is CRa. This is the first report on the molecular characterization of a clubroot Resistance gene in Brassicaceae and of the disease resistance gene in B. rapa.ArticlePLANT MOLECULAR BIOLOGY. 80(6):621-629 (2012)journal articl

Longer and better lives for patients with atrial fibrillation: the 9th AFNET/EHRA consensus conference.

AIMS: Recent trial data demonstrate beneficial effects of active rhythm management in patients with atrial fibrillation (AF) and support the concept that a low arrhythmia burden is associated with a low risk of AF-related complications. The aim of this document is to summarize the key outcomes of the 9th AFNET/EHRA Consensus Conference of the Atrial Fibrillation NETwork (AFNET) and the European Heart Rhythm Association (EHRA). METHODS AND RESULTS: Eighty-three international experts met in Münster for 2 days in September 2023. Key findings are as follows: (i) Active rhythm management should be part of the default initial treatment for all suitable patients with AF. (ii) Patients with device-detected AF have a low burden of AF and a low risk of stroke. Anticoagulation prevents some strokes and also increases major but non-lethal bleeding. (iii) More research is needed to improve stroke risk prediction in patients with AF, especially in those with a low AF burden. Biomolecules, genetics, and imaging can support this. (iv) The presence of AF should trigger systematic workup and comprehensive treatment of concomitant cardiovascular conditions. (v) Machine learning algorithms have been used to improve detection or likely development of AF. Cooperation between clinicians and data scientists is needed to leverage the potential of data science applications for patients with AF. CONCLUSIONS: Patients with AF and a low arrhythmia burden have a lower risk of stroke and other cardiovascular events than those with a high arrhythmia burden. Combining active rhythm control, anticoagulation, rate control, and therapy of concomitant cardiovascular conditions can improve the lives of patients with AF

Diagnosis of obstructive coronary artery disease using computed tomography angiography in patients with stable chest pain depending on clinical probability and in clinically important subgroups: Meta-analysis of individual patient data

Objective To determine whether coronary computed tomography angiography (CTA) should be performed in patients with any clinical probability of coronary artery disease (CAD), and whether the diagnostic performance differs between subgroups of patients. Design Prospectively designed meta-analysis of individual patient data from prospective diagnostic accuracy studies. Data sources Medline, Embase, and Web of Science for published studies. Unpublished studies were identified via direct contact with participating investigators. Eligibility criteria for selecting studies Prospective diagnostic accuracy studies that compared coronary CTA with coronary angiography as the reference standard, using at least a 50% diameter reduction as a cutoff value for obstructive CAD. All patients needed to have a clinical indication for coronary angiography due to suspected CAD, and both tests had to be performed in all patients. Results had to be provided using 2×2 or 3×2 cross tabulations for the comparison of CTA with coronary angiography. Primary outcomes were the positive and negative predictive values of CTA as a function of clinical pretest probability of obstructive CAD, analysed by a generalised linear mixed model; calculations were performed including and excluding non-diagnostic CTA results. The no-treat/treat threshold model was used to determine the range of appropriate pretest probabilities for CTA. The threshold model was based on obtained post-test probabilities of less than 15% in case of negative CTA and above 50% in case of positive CTA. Sex, angina pectoris type, age, and number of computed tomography detector rows were used as clinical variables to analyse the diagnostic performance in relevant subgroups. Results Individual patient data from 5332 patients from 65 prospective diagnostic accuracy studies were retrieved. For a pretest probability range of 7-67%, the treat threshold of more than 50% and the no-treat threshold of less than 15% post-test probability were obtained using CTA. At a pretest probability of 7%, the positive predictive value of CTA was 50.9% (95% confidence interval 43.3% to 57.7%) and the negative predictive value of CTA was 97.8% (96.4% to 98.7%); corresponding values at a pretest probability of 67% were 82.7% (78.3% to 86.2%) and 85.0% (80.2% to 88.9%), respectively. The overall sensitivity of CTA was 95.2% (92.6% to 96.9%) and the specificity was 79.2% (74.9% to 82.9%). CTA using more than 64 detector rows was associated with a higher empirical sensitivity than CTA using up to 64 rows (93.4% v 86.5%, P=0.002) and specificity (84.4% v 72.6%, P<0.001). The area under the receiver-operating-characteristic curve for CTA was 0.897 (0.889 to 0.906), and the diagnostic performance of CTA was slightly lower in women than in with men (area under the curve 0.874 (0.858 to 0.890) v 0.907 (0.897 to 0.916), P<0.001). The diagnostic performance of CTA was slightly lower in patients older than 75 (0.864 (0.834 to 0.894), P=0.018 v all other age groups) and was not significantly influenced by angina pectoris type (typical angina 0.895 (0.873 to 0.917), atypical angina 0.898 (0.884 to 0.913), non-anginal chest pain 0.884 (0.870 to 0.899), other chest discomfort 0.915 (0.897 to 0.934)). Conclusions In a no-treat/treat threshold model, the diagnosis of obstructive CAD using coronary CTA in patients with stable chest pain was most accurate when the clinical pretest probability was between 7% and 67%. Performance of CTA was not influenced by the angina pectoris type and was slightly higher in men and lower in older patients. Systematic review registration PROSPERO CRD42012002780

Impact of fasting glucose on electrocardiographic left ventricular hypertrophy in an elderly general population

Objective. To evaluate relationships between fasting plasma glucose (FPG), other cardiovascular risk markers and left ventricular hypertrophy (LVH) as detected by electrocardiography. Methods. Subjects were selected randomly from groups defi ned by FPG. Traditional risk markers were assessed. LVH was defi ned by either Cornell voltage -duration product (CP) or Sokolow -Lyon voltage combination (SL), and univariate and multivariable regressions were performed in search of explanatory factors for the presence of LVH and the values of CP and SL. Results. Of the 1759 subjects included, 1007 had a history of cardiovascular disease and/or medical treatment, while 752 subjects appeared to be healthy. We found an independent association between FPG and LVH (odds ratio 1.152, p = 0.042] as well as continuous CP (beta = 0.126, p = 0.007) in healthy men. As expected, we found an association between systolic blood pressure and LVH (odds ratio 1.020, p < 0.001) among healthy subjects, but only in subjects with FPG < 6 mmol/l (p = 0.04 for interaction). Conclusions. We found an independent association between FPG and LVH in healthy men, and no potentiating effect by FPG on the impact of hypertension

Accelerometer-assessed physical behavior and the association with clinical outcomes in implantable cardioverter-defibrillator recipients: A systematic review

Background: Current implantable cardioverter-defibrillator (ICD) devices are equipped with a device-embedded accelerometer capable of capturing physical activity (PA). In contrast, wearable accelerometer-based methods enable the measurement of physical behavior (PB) that encompasses not only PA but also sleep behavior, sedentary time, and rest-activity patterns. Objective: This systematic review evaluates accelerometer-based methods used in patients carrying an ICD or at high risk of sudden cardiac death. Methods: Papers were identified via the OVID MEDLINE and OVID EMBASE databases. PB could be assessed using a wearable accelerometer or an embedded accelerometer in the ICD. Results: A total of 52 papers were deemed appropriate for this review. Out of these studies, 30 examined device-embedded accelerometry (189,811 patients), 19 examined wearable accelerometry (1601 patients), and 3 validated wearable accelerometry against device-embedded accelerometry (106 patients). The main findings were that a low level of PA after implantation of the ICD and a decline in PA were both associated with an increased risk of mortality, heart failure hospitalization, and appropriate ICD shock. Second, PA was affected by cardiac factors (eg, onset of atrial fibrillation, ICD shocks) and noncardiac factors (eg, seasonal differences, societal factors). Conclusion: This review demonstrated the potential of accelerometer-measured PA as a marker of clinical deterioration and ventricular arrhythmias. Notwithstanding that the evidence of PB assessed using wearable accelerometry was limited, there seems to be potential for accelerometers to improve early warning systems and facilitate preventative and proactive strategies