Orthostatic test shows higher systolic blood pressure and sympathetic response in uncomplicated type 1 diabetes patients with normal V̇O vs. healthy controls.

Purpose: Cardiovascular autonomic neuropathy remains underdiagnosed in type 1 diabetes mellitus, posing a risk for severe complications, particularly in patients with lowered V̇O, compared to controls. This study aimed to determine whether heart rate variability during cardiovascular autonomic reflex tests reveals early signs of cardiovascular autonomic neuropathy in patients with uncomplicated type 1 diabetes mellitus and normal cardiovascular fitness, compared to healthy controls.

Methods: A type 1 diabetes mellitus group (n = 14) with no other diagnosed diseases (diabetes duration 15 ± 7 years) and a control group (n = 31) underwent deep breathing test, passive orthostatic test, and cardiopulmonary exercise test.

tRNA-Derived Fragments as Biomarkers in Bladder Cancer.

Bladder cancer (BC) diagnosis is reliant on cystoscopy, an invasive procedure associated with urinary tract infections. This has sparked interest in identifying noninvasive biomarkers in body fluids such as blood and urine. A source of biomarkers in these biofluids are extracellular vesicles (EVs), nanosized vesicles that contain a wide array of molecular cargo, including small noncoding RNA such as transfer RNA-derived fragments (tRF) and microRNA.

LSD1 drives intestinal epithelial maturation and controls small intestinal immune cell composition independent of microbiota in a murine model.

Postnatal development of the gastrointestinal tract involves the establishment of the commensal microbiota, the acquisition of immune tolerance via a balanced immune cell composition, and maturation of the intestinal epithelium. While studies have uncovered an interplay between the first two, less is known about the role of the maturing epithelium. Here we show that intestinal-epithelial intrinsic expression of lysine-specific demethylase 1A (LSD1) is necessary for the postnatal maturation of intestinal epithelium and maintenance of this developed state during adulthood.

Retroelement decay by the exonuclease XRN1 is a viral mimicry dependency in cancer.

Viral mimicry describes the immune response induced by endogenous stimuli such as double-stranded RNA (dsRNA) from endogenous retroelements. Activation of viral mimicry has the potential to kill cancer cells or augment anti-tumor immune responses. Here, we systematically identify mechanisms of viral mimicry adaptation associated with cancer cell dependencies.

deficient mice exhibit heightened goblet cell effector expression in the colon and increased resistance to chronic infection.

Intestinal epithelial homeostasis is maintained by intrinsic and extrinsic signals. The extrinsic signals include those provided by mesenchymal cell populations that surround intestinal crypts and is further facilitated by the extracellular matrix (ECM), which is modulated by proteases such as matrix metalloproteinases (MMPs). Extrinsic signals ensure an appropriate balance between intestinal epithelial proliferation and differentiation.

Human endogenous oxytocin and its neural correlates show adaptive responses to social touch based on recent social context.

Both oxytocin (OT) and touch are key mediators of social attachment. In rodents, tactile stimulation elicits the endogenous release of OT, potentially facilitating attachment and other forms of prosocial behavior, yet the relationship between endogenous OT and neural modulation remains unexplored in humans. Using a serial sampling of plasma hormone levels during functional neuroimaging across two successive social interactions, we show that contextual circumstances of social touch influence not only current hormonal and brain responses but also responses.

Na/K‑ATPase subunit α3 expression is associated with the efficacy of digitoxin treatment in pancreatic cancer cells.

The alpha subunits (ATP1A1-3) of Na/K-ATPase binds digitoxin with varying affinity. The expression levels of these subunits dictate the anticancer effects of digitoxin. In the present study, three pancreatic cancer cell lines, AsPC-1, Panc-1 and CFPAC-1, were used to investigate the effects of digitoxin in relation to the expression of the subunits ATP1A1 and ATP1A3.

Characterisation of Colorectal Cancer Cell Lines through Proteomic Profiling of Their Extracellular Vesicles.

Colorectal cancer (CRC) is one of the most prevalent cancers, driven by several factors including deregulations in intracellular signalling pathways. Small extracellular vesicles (sEVs) are nanosized protein-packaged particles released from cells, which are present in liquid biopsies. Here, we characterised the proteome landscape of sEVs and their cells of origin in three CRC cell lines HCT116, HT29 and SW620 to explore molecular traits that could be exploited as cancer biomarker candidates and how intracellular signalling can be assessed by sEV analysis instead of directly obtaining the cell of origin itself.

Endogenous retroelements as alarms for disruptions to cellular homeostasis.

Endogenous retroelements are DNA sequences which can duplicate and move to new locations in the genome. Actively moving endogenous retroelements can be disruptive to the host, and their expression is therefore often repressed. Interestingly, drugs that disrupt the repression of endogenous retroelements show promise for treating cancer.

Digitoxin Affects Metabolism, ROS Production and Proliferation in Pancreatic Cancer Cells Differently Depending on the Cell Phenotype.

Digitoxin has repeatedly shown to have negative effects on cancer cell viability; however, the actual mechanism is still unknown. In this study, we investigated the effects of digitoxin (1-100 nM) in four pancreatic cancer cell lines, BxPC-3, CFPAC-1, Panc-1, and AsPC-1. The cell lines differ in their KRAS/BRAF mutational status and primary tumor or metastasis origin.

BMP signaling in the intestinal epithelium drives a critical feedback loop to restrain IL-13-driven tuft cell hyperplasia.

The intestinal tract is a common site for various types of infections including viruses, bacteria, and helminths, each requiring specific modes of immune defense. The intestinal epithelium has a pivotal role in both immune initiation and effector stages, which are coordinated by lymphocyte cytokines such as IFNγ, IL-13, and IL-22. Here, we studied intestinal epithelial immune responses using organoid image analysis based on a convolutional neural network, transcriptomic analysis, and in vivo infection models.

The association between chronotype and sleep quality among female home care workers performing shift work.

There is a scarcity of evidence on the association between shift work, sleeping parameters, heart rate variability (HRV), and chronotype, i.e., morningness and eveningness.

Smooth muscle-specific MMP17 (MT4-MMP) regulates the intestinal stem cell niche and regeneration after damage.

Smooth muscle is an essential component of the intestine, both to maintain its structure and produce peristaltic and segmentation movements. However, very little is known about other putative roles that smooth muscle cells may have. Here, we show that smooth muscle cells may be the dominant suppliers of BMP antagonists, which are niche factors essential for intestinal stem cell maintenance.

Intestinal epithelial tuft cell induction is negated by a murine helminth and its secreted products.

Helminth parasites are adept manipulators of the immune system, using multiple strategies to evade the host type 2 response. In the intestinal niche, the epithelium is crucial for initiating type 2 immunity via tuft cells, which together with goblet cells expand dramatically in response to the type 2 cytokines IL-4 and IL-13. However, it is not known whether helminths modulate these epithelial cell populations.

Differentially Expressed Extracellular Vesicle-Contained microRNAs before and after Transurethral Resection of Bladder Tumors.

Bladder cancer (BC) is currently diagnosed and monitored by cystoscopy, a costly and invasive procedure. Potential biomarkers in urine, blood, and, more recently, extracellular vesicles (EVs), have been explored as non-invasive alternatives for diagnosis and surveillance of BC. EVs are nanovesicles secreted by most cell types containing diverse molecular cargo, including different types of small RNAs, such as microRNA (miRNA).

Intestinal-epithelial LSD1 controls goblet cell maturation and effector responses required for gut immunity to bacterial and helminth infection.

Infectious and inflammatory diseases in the intestine remain a serious threat for patients world-wide. Reprogramming of the intestinal epithelium towards a protective effector state is important to manage inflammation and immunity and can be therapeutically targeted. The role of epigenetic regulatory enzymes within these processes is not yet defined.

A Semi-automated Organoid Screening Method Demonstrates Epigenetic Control of Intestinal Epithelial Differentiation.

Intestinal organoids are an excellent model to study epithelial biology. Yet, the selection of analytical tools to accurately quantify heterogeneous organoid cultures remains limited. Here, we developed a semi-automated organoid screening method, which we applied to a library of highly specific chemical probes to identify epigenetic regulators of intestinal epithelial biology.

Genetic risk-factors for anxiety in healthy individuals: polymorphisms in genes important for the HPA axis.

Background: Two important aspects for the development of anxiety disorders are genetic predisposition and alterations in the hypothalamic-pituitary-adrenal (HPA) axis. In order to identify genetic risk-factors for anxiety, the aim of this exploratory study was to investigate possible relationships between genetic polymorphisms in genes important for the regulation and activity of the HPA axis and self-assessed anxiety in healthy individuals.

Methods: DNA from 72 healthy participants, 37 women and 35 men, were included in the analyses.

Plant Stanol Esters Reduce LDL (Low-Density Lipoprotein) Aggregation by Altering LDL Surface Lipids: The BLOOD FLOW Randomized Intervention Study.

Objective: Plant stanol ester supplementation (2-3 g plant stanols/d) reduces plasma LDL (low-density lipoprotein) cholesterol concentration by 9% to 12% and is, therefore, recommended as part of prevention and treatment of atherosclerotic cardiovascular disease. In addition to plasma LDL-cholesterol concentration, also qualitative properties of LDL particles can influence atherogenesis. However, the effect of plant stanol ester consumption on the proatherogenic properties of LDL has not been studied.

Estimation of Beat-to-Beat Interval and Systolic Time Intervals Using Phono- and Seismocardiograms.

Systolic time intervals Pre-Ejection Period (PEP) and Left Ventricular Ejection Time (LVET) are widely used indicators of cardiac functions. While accurate assessment of them requires costly equipment such as echocardiography devices, a satisfactory estimation can be done by analyzing signals from simple accelerometer and microphone attached to human chest. This paper reports a study where heart rate and the systolic intervals were derived from phonocardiogram (PCG) and seismocardiogram (SCG) simultaneously.

Deep learning for prediction of cardiac indices from photoplethysmographic waveform: A virtual database approach.

Deep learning methods combined with large datasets have recently shown significant progress in solving several medical tasks. However, collecting and annotating large datasets can be a very cumbersome and expensive task. We tackle these problems with a virtual database approach where training data is generated using computer simulations of related phenomena.

Effects of occupational cobalt exposure on the heart in the production of cobalt and cobalt compounds: a 6-year follow-up.

Objective: It has been suspected that cobalt is toxic to the heart. It can cause cardiotoxicity in heavily exposed humans and in experimental systems. The issue of interest for this study is whether cobalt also affects the myocardium at occupational exposure levels.

Clinical Characteristics of Disability in Patients with Indoor Air-Related Environmental Intolerance.

Background: Chronic nonspecific symptoms attributed to indoor nonindustrial work environments are common and may cause disability, but the medical nature of this disability is unclear. The aim was to medically characterize the disability manifested by chronic, recurrent symptoms and restrictions to work participation attributed to low-level indoor pollutants at workplace and whether the condition shares features with idiopathic environmental intolerance.

Methods: We investigated 12 patients with indoor air-related work disability.

Pulse transit time estimation of aortic pulse wave velocity and blood pressure using machine learning and simulated training data.

Recent developments in cardiovascular modelling allow us to simulate blood flow in an entire human body. Such model can also be used to create databases of virtual subjects, with sizes limited only by computational resources. In this work, we study if it is possible to estimate cardiovascular health indices using machine learning approaches.