Diabetes mellitus (DM) is a common disease worldwide. There is a strong association between DM and neurovascular and neurodegenerative disorders. The first group mainly consists of diabetic retinopathy, diabetic neuropathy and stroke, whereas, the second group includes Alzheimer’s disease, Parkinson’s disease, mild cognitive impairment and dementia. The aforementioned diseases have a common pathophysiological background including insulin resistance, oxidative stress, atherosclerosis and vascular injury. The increasing prevalence of neurovascular and neurodegenerative disorders among diabetic patients has resulted in an urgent need to develop biomarkers for their prediction and/or early detection. The aim of this review is to present the potential application of the most promising biomarkers of diabetes-related neurodegenerative and neurovascular disorders, including amylin, β-amyloid, C-reactive protein (CRP), dopamine, gamma-glutamyl transferase (GGT), glycogen synthase kinase 3β, homocysteine, microRNAs (mi-RNAs), paraoxonase 1, phosphoinositide 3-kinases, tau protein and various growth factors. The most clinically promising biomarkers of neurovascular and neurodegenerative complications in DM are hsCRP, GGT, homocysteine and miRNAs. However, all biomarkers discussed in this review could become a part of the potential multi-biomarker screening panel for diabetic patients at risk of neurovascular and neurodegenerative complications.

Background: Increased inflammation activates blood coagulation system, higher platelet activation plays a key role in the pathophysiology of ischemic stroke (IS). During platelet activation and aggregation process, platelets may cause increased release of several proinflammatory, and prothrombotic mediators, including microRNAs (miRNAs) and extracellular vesicles (EVs). In the current study we aimed to assess circulating miRNAs profile related to platelet function and inflammation and circulating EVs from platelets, leukocytes, and endothelial cells to analyse their diagnostic and predictive utility in patients with acute IS. Methods: The study population consisted of 28 patients with the diagnosis of the acute IS. The control group consisted of 35 age- and gender-matched patients on acetylsalicylic acid (ASA) therapy without history of stroke and/or TIA with established stable coronary artery disease (CAD) and concomitant cardiovascular risk factors. Venous blood samples were collected from the control group and patients with IS on ASA therapy (a) 24 h after onset of acute IS, (b) 7-days following index hospitalization. Flow cytometry was used to determine the concentration of circulating EVs subtypes (from platelets, leukocytes, and endothelial cells) in platelet-depleted plasma and qRT-PCR was used to determine several circulating plasma miRNAs (miR-19a-3p, miR-186-5p and let-7f). Results: Patients with high platelet reactivity (HPR, based on arachidonic acid-induced platelet aggregometry) had significantly elevated platelet-EVs (CD62+) and leukocyte-EVs (CD45+) concentration compared to patients with normal platelet reactivity at the day of 1 acute-stroke (p = 0.012, p = 0.002, respectively). Diagnostic values of baseline miRNAs and EVs were evaluated with receiver operating characteristic (ROC) curve analysis. The area under the ROC curve for miR-19a-3p was 0.755 (95% CI, 0.63–0.88) p = 0.004, for let-7f, it was 0.874 (95% CI, 0.76–0.99) p = 0.0001; platelet-EVs was 0.776 (95% CI, 0.65–0.90) p = 0.001, whereas for leukocyte-EVs, it was 0.715 (95% CI, 0.57–0.87) p = 0.008. ROC curve showed that pooling the miR-19a-3p expressions, platelet-EVs, and leukocyte-EVs concentration yielded a higher AUC than the value of each individual biomarker as AUC was 0.893 (95% CI, 0.79–0.99). Patients with moderate stroke had significantly elevated miR-19a-3p expression levels compared to patients with minor stroke at the first day of IS. (AUC: 0.867, (95% CI, 0.74–0.10) p = 0.001). Conclusion: Combining different biomarkers of processes underlying IS pathophysiology might be beneficial for early diagnosis of ischemic events. Thus, we believe that in the future circulating biomarkers might be used in the prehospital phase of IS. In particular, circulating plasma EVs and non-coding RNAs including miRNAs are interesting candidates as bearers of circulating biomarkers due to their high stability in the blood and making them highly relevant biomarkers for IS diagnostics.

BackgroundUterine myoactivity is crucial for successful reproductive performance of the sow. Spontaneous contractions of the uterus are strictly controlled and coordinated. Uterine electromyographic (EMG) activity undergoes hormonal regulation with rapid and long-term effects. What is more, interstitial Cajal-like Cells (ICLC) appear essential for smooth muscle contractility in the reproductive tract where they are suspected to be playing a major role in generating, coordinating, modulating and synchronizing slow triggering waves. The aim of this study was to investigate the myoelectrical activity of sow’s uterus during estrus cycle.ResultsStudy was conducted on 10 Polish Landrace sows. Propagation mechanisms and their connection with the uterine EMG activity were considered in correlation with expression of c-kit, progesterone and oxytocin receptors of the non-pregnant sow. ICLC were labeled with antibody directed against c-kit receptor and visualized by confocal microscopy and scanning cytometer for positive cells percentage assessment. EMG signal was recorded directly from the myometrium with telemetry transmitters and electrodes located in different topographic regions of reproductive tracts. The stages of estrus cycle were determined by monitoring levels of luteinizing hormone, progesterone and estrogen with radioimmunoassays. Significant differences of the EMG signal parameters between diestrus and estrus and the correlations with density of labelled receptors were demonstrated. Moreover, the electrophysiological studies indicated that ICLC in the myometrium in the tip of uterine horn may participate in the regulation of slow waves duration and frequency.ConclusionsThe pattern of EMG signal propagation in the wall of the non-pregnant porcine uterus occurs in an orderly, bidirectional fashion and at distinctive speed, with no differences between diestrus and estrus.

New Findings What is the central question of this study?Does oestrous cycle synchronization influence myoelectrical activity of porcine myometrium? What is the main finding and its importance?Exogenous hormones used to synchronize oestrus in pigs altered myoelectrical activity, which was effectively modelled. Higher‐order multivariate statistic modelling provided evidence of similar activity in both types of oestrus, but a larger order of EMG signals during induced oestrus. Higher‐order statistical analysis of the probabilistic model suggests the beginning of the early follicular phase and the mid‐luteal phase to be most important in evaluation of the natural patterns of myoelectrical activity. Higher‐order multivariate cumulants are more informative than classical statistics in characterization of myoelectrical activity changes in porcine myometrium. Abstract In pig production units, control of the oestrous cycle and synchronization of ovulation have become routine herd management procedures. During the oestrous cycle, in both induced and spontaneous conditions, the ovaries and the uterus undergo hormone‐dominated physiological changes, which are consistent with the hypothesis that there is a functional role of uterine contractions in promoting fertilization. We have used electromyography to determine whether the use of exogenous hormones, such as equine chorionic gonadotrophin and human chorionic gonadotrophin, which have the potential to control the timing of ovulation in female pigs, changes the multivariate relationships between parameters of electrical bursts and modulates the patterns of myoelectrical activity. We used the mathematical approach of higher‐order multivariate cumulants in complex modelling of the myometrial electrical activity. The experiment was conducted on 12 mature Polish Landrace sows, and uterine activity was recorded during both spontaneous and induced oestrous cycles. The burst parameters were determined using six features in the time domain and, after Fast Fourier transformation, in the frequency domain. Evaluation of myoelectrical activity patterns was conducted based on classical univariate statistical methods and multivariate probabilistic modelling. The classical statistical approach indicated weaker myoelectrical activity after hormonal stimulation, whereas the higher‐order multivariate statistical model showed evidence of similar status of activity and a larger order of signals during induced oestrus. Routine oestrous cycle synchronization affects the multivariate probabilistic model of myometrial electrical activity.

Acetylsalicylic acid (ASA) is one of the most frequently used medications worldwide. Yet, the main indications for ASA are the atherosclerosis-based cardiovascular diseases, including coronary artery disease (CAD). Despite the increasing number of percutaneous procedures to treat CAD, coronary artery bypass grafting (CABG) remains the treatment of choice in patients with multivessel CAD and intermediate or high anatomical lesion complexity. Taking into account that CABG is a potent activator of inflammation, ASA is an important part in the postoperative therapy, not only due to ASA antiplatelet action, but also as an anti-inflammatory agent. Additional benefits of ASA after CABG include anticancerogenic, hypotensive, antiproliferative, anti-osteoporotic, and neuroprotective effects, which are especially important in patients after CABG, prone to hypertension, graft occlusion, atherosclerosis progression, and cognitive impairment. Here, we discuss the pleiotropic effects of ASA after CABG and provide insights into the mechanisms underlying the benefits of treatment with ASA, beyond platelet inhibition. Since some of ASA pleiotropic effects seem to increase the risk of bleeding, it could be considered a starting point to investigate whether the increase of the intensity of the treatment with ASA after CABG is beneficial for the CABG group of patients.