Effects of renal denervation on the course of cardiorenal syndrome: insight from studies with fawn-hooded hypertensive rats.

Combination of chronic kidney disease (CKD) and heart failure (HF) results in extremely high morbidity and mortality. The current guideline-directed medical therapy is rarely effective and new therapeutic approaches are urgently needed. The study was designed to examine if renal denervation (RDN) will exhibit long-standing beneficial effects on the HF- and CKD-related morbidity and mortality.

Accumulation of chlorinated paraffins in adipocytes is determined by cellular lipid content and chlorination level.

Chlorinated paraffins (CPs) are environmental pollutants extensively used in industries. While the use of short-chain chlorinated paraffins (SCCPs) has been restricted since 2017, the use of medium-chain chlorinated paraffins (MCCPs) has risen as their replacement. Due to lipophilic character, it can be expected that CPs enter the cells; however, the in vitro accumulation potential of CPs remains poorly understood.

Multivariate patterns among multimodal neuroimaging and clinical, cognitive, and daily functioning characteristics in bipolar disorder.

Individuals with bipolar disorder (BD) show heterogeneity in clinical, cognitive, and daily functioning characteristics, which challenges accurate diagnostics and optimal treatment. A key goal is to identify brain-based biomarkers that inform patient stratification and serve as treatment targets. The objective of the present study was to apply a data-driven, multivariate approach to quantify the relationship between multimodal imaging features and behavioral phenotypes in BD.

Gut dysbiosis-induced vitamin B6 metabolic disorder contributes to chronic stress-related abnormal behaviors in a cortisol-independent manner.

Chronic stress can result in various conditions, including psychological disorders, neurodegenerative diseases, and accelerated brain aging. Gut dysbiosis potentially contributes to stress-related brain disorders in individuals with chronic stress. However, the causal relationship and key factors between gut dysbiosis and brain disorders in chronic stress remain elusive, particularly under non-sterile conditions.

Sympathetic nervous system inhibition enhances cardiac metabolism and improves hemodynamics and glucose-insulin dynamics in obese and lean rat models.

This study aimed to investigate the effects of chronic sympathoinhibition on glucose uptake by the myocardium and by the skeletal muscle in an animal model of obesity associated with leptin signaling deficiency. 6 obese Zucker rats (OZR) and 6 control Lean Zucker rats (LZR) were studied during basal conditions, chronic clonidine administration (30 days, 300 µg/kg), and washout recovery period. Glucose uptake in the myocardium and in the skeletal muscle was measured using positron emission tomography (PET) and 2-[18F] fluoro-2-deoxy-D-glucose ([18F]FDG).

Unraveling ptosis: A comprehensive review of clinical manifestations, genetics, and treatment.

Ptosis is defined as an abnormally low-lying upper eyelid margin on the primary gaze, generally resulting from a congenital or acquired abnormality of the nerves or muscles that control the eyelid. Ptosis can occur alone or concurrently as an ocular or systemic syndrome, and the prevalence of ptosis varies among different countries and populations. Isolated ptosis typically causes aesthetic problems in patients and can lead to functional ophthalmic problems in severe cases.

Probiotics prevent pegylated liposomal doxorubicin-associated hand-foot syndrome and oral mucositis of breast cancer patients following surgery and chemotherapy:a randomized placebo-controlled trial.

Background: Hand-foot syndrome (HFS) and oral mucositis (OM) are common adverse events during cancer chemotherapy and can significantly decrease patients' quality of life and chemotherapy adaptation, however, prevention strategies of these complications yet to be established.

Methods: Patients with stage I-III breast cancer, who had surgery and needed pegylated liposomal doxorubicin (PLD)-based adjuvant chemotherapy were screened, recruited and randomly assigned to receive either probiotics or placebo (three capsules, twice/day) treatment during the course of chemotherapy from Nov. 2019 to Aug.

Resilience and charge-dependent fibrillation of functional amyloid: Interactions of Pseudomonas biofilm-associated FapB and FapC amyloids.

FapC and FapB are biofilm-associated amyloids involved in the virulence of Pseudomonas and other bacteria. We herein demonstrate their exceptional thermal and chemical resilience, suggesting that their biofilm structures might withstand standard sterilization, thereby contributing to the persistence of Pseudomonas aeruginosa infections. Our findings also underscore the impact of environmental factors on functional amyloid in Pseudomonas (Fap) proteins, suggesting that orthologs in different Pseudomonas strains adapt to specific environments and roles.

Chitosan-Electrospun Fibers Encapsulating Norfloxacin: The Impact on the Biochemical, Oxidative and Immunological Profile in a Rats Burn Model.

This study investigates the impact of chitosan-based nanofibers on burn wound healing in a rat model. Two formulations of chitosan nanofibers were prepared through electrospinning. The formulations were then incorporated with different amounts of norfloxacin and underwent surface modifications with 2-formylphenylboronic acid.

Tolerability, safety, and pharmacokinetics of GR1603 injection in healthy subjects: a randomized, double-blind, placebo-controlled single-dose escalation clinical trial.

Background: GR1603 is a monoclonal antibody targeting the type I interferon receptor. The aim of this study was to evaluate the safety, tolerability, pharmacokinetics, immunogenicity and pharmacodynamics of GR1603 in healthy volunteers.

Methods: Healthy adults (≥18 years old) were enrolled in a placebo control, dose-escalation Phase I clinical trial receiving a single injectable dose of GR1603.

Soluble guanylyl cyclase stimulators and activators: Promising drugs for the treatment of hypertension?

Nitric oxide (NO)-stimulated cyclic guanosine monophosphate (cGMP) is a key regulator of cardiovascular health, as NO-cGMP signalling is impaired in diseases like pulmonary hypertension, heart failure and chronic kidney disease. The development of NO-independent sGC stimulators and activators provide a novel therapeutic option to restore altered NO signalling. sGC stimulators have been already approved for the treatment of pulmonary arterial hypertension (PAH), chronic thromboembolic pulmonary hypertension (CTEPH), and chronic heart failure (HFrEF), while sGC activators are currently in phase-2 clinical trials for CKD.

The matrix protease ADAMTS1 is transcriptionally activated by KLF6 and contributes to cardiac fibrosis in non-ischemic cardiomyopathy.

Aims: Aberrant cardiac fibrosis, defined as excessive production and deposition of extracellular matrix (ECM), is mediated by myofibroblasts. ECM-producing myofibroblasts are primarily derived from resident fibroblasts during cardiac fibrosis. The mechanism underlying fibroblast-myofibroblast transition is not fully understood.

A versatile in vivo platform for reversible control of transgene expression in adult tissues.

Temporal control of transgenes has advanced biomedical interventions, including in vivo reprogramming, often utilizing the doxycycline (Dox)-mediated Tet-ON system. Here, we developed the Dox-mediated Tet-ON or complementary Tet-OFF counterpart to thoroughly investigate spatial and temporal transgene regulation in adult tissues, revealing inherent limitations and unexpected capabilities of each system. In stark contrast with the Tet-ON system, which was effective only in particular tissues and cell types, primarily epithelial cells, the Tet-OFF system proved capable of gene induction across diverse cell types.

PACS2/CPT1A/DHODH signaling promotes cardiomyocyte ferroptosis in diabetic cardiomyopathy.

Objectives: The pathophysiology of diabetic cardiomyopathy (DCM) is a phenomenon of great interest, but its clinical problems have not yet been effectively addressed. Recently, the mechanism of ferroptosis in the pathophysiology of various diseases, including DCM, has attracted widespread attention. Here, we explored the role of PACS2 in ferroptosis in DCM through its downregulation of PACS2 expression.

Female prediabetic rats are protected from vascular dysfunction: the role of nitroso and sulfide signaling.

Background: The activity of perivascular adipose tissue (PVAT), a specific deposit of adipose tissue surrounding blood vessels, could contribute to sex differences in vascular tone control, particularly in dyslipidemic disorders; however, the mutual associations remain unclear. This study aimed to evaluate the relationships among sex, PVAT and vascular function in Wistar and hereditary hypertriglyceridemic (HTG) rats. Vasoactive responses of the isolated thoracic aorta with preserved or removed PVAT were compared in adult male and female Wistar and HTG rats, and the roles of nitric oxide (NO), hydrogen sulfide (HS), cyclooxygenase (COX) and inflammatory signaling in vascular function were monitored in females.

CRISPR Diagnostics for Quantification and Rapid Diagnosis of Myotonic Dystrophy Type 1 Repeat Expansion Disorders.

Repeat expansion disorders, exemplified by myotonic dystrophy type 1 (DM1), present challenges in diagnostic quantification because of the variability and complexity of repeat lengths. Traditional diagnostic methods, including PCR and Southern blotting, exhibit limitations in sensitivity and specificity, necessitating the development of innovative approaches for precise and rapid diagnosis. Here, we introduce a CRISPR-based diagnostic method, REPLICA (peat-rimed ocating of nherited disease by s3), for the quantification and rapid diagnosis of DM1.

Plasma p-tau181 and GFAP reflect 7T MR-derived changes in Alzheimer's disease: A longitudinal study of structural and functional MRI and MRS.

Background: Associations between longitudinal changes of plasma biomarkers and cerebral magnetic resonance (MR)-derived measurements in Alzheimer's disease (AD) remain unclear.

Methods: In a study population (n = 127) of healthy older adults and patients within the AD continuum, we examined associations between longitudinal plasma amyloid beta 42/40 ratio, tau phosphorylated at threonine 181 (p-tau181), glial fibrillary acidic protein (GFAP), neurofilament light chain (NfL), and 7T structural and functional MR imaging and spectroscopy using linear mixed models.

Results: Increases in both p-tau181 and GFAP showed the strongest associations to 7T MR-derived measurements, particularly with decreasing parietal cortical thickness, decreasing connectivity of the salience network, and increasing neuroinflammation as determined by MR spectroscopy (MRS) myo-inositol.

Transgenic rat with ubiquitous expression of angiotensin-(1-7)-producing fusion protein: a new tool to study the role of protective arm of the renin-angiotensin system in the pathophysiology of cardio-renal diseases.

The aim of the present study was to assess systemic circulatory and tissue activities of both the classical arm and of the alternative arm of the renin-angiotensin system (RAS) in a new transgenic rat line (TG7371) that expresses angiotensin-(1-7) (ANG 1-7)-producing fusion protein; the results were compared with the activities measured in control transgene-negative Hannover Sprague-Dawley (HanSD) rats. Plasma and tissue concentrations of angiotensin II (ANG II) and ANG 1-7, and kidney mRNA expressions of receptors responsible for biological actions of ANG II and ANG 1-7 [i.e.

Recompensation of Liver Cirrhosis by TIPS Reduces Epithelial Cell Death Markers, Translating Into Improved Clinical Outcome.

Background And Aims: Portal hypertension is the main pathophysiological driver of decompensation in patients with liver cirrhosis. Epithelial cell death markers, m30 and m65, correlate with hepatic injury and predict outcomes across various stages of liver disease. We aim (i) to evaluate whether portal hypertension itself contributes to liver outcome-relevant epithelial injury, and (ii) to analyse the capacity of m30/m65 to predict outcome in patients receiving a transjugular intrahepatic portosystemic shunt (TIPS) for refractory ascites.

Assessment of Metabolic Syndrome in Patients with Chronic Obstructive Pulmonary Disease: A 6-Month Follow-Up Study.

Background/objectives: The association between chronic obstructive pulmonary disease (COPD) and metabolic syndrome (MetS) is a common one, with long-term therapeutic and prognostic impact. In view of the high pulmonary and cardiovascular morbidity and mortality, self-management contributes to decreasing the risk of an acute cardiac event or pulmonary decompensation.

Methods: We conducted a prospective cohort study on 100 patients admitted to Iasi Clinical Rehabilitation Hospital who were divided into two groups according to the presence (67 patients) or absence (33 patients) of MetS.

Targeting the chromatin remodeling protein BRG1 in liver fibrosis: Mechanism and translational potential.

Aims: Liver fibrosis is characterized by excessive deposition of extracellular matrix (ECM) proteins in the interstitia. Hepatic stellate cells (HSCs) are considered the major source for ECM-producing myofibroblasts contributing to liver fibrosis. The molecular mechanism whereby HSC-myofibroblast transition is regulated remains incompletely understood.

Deep learning-based whole-brain B -mapping at 7T.

Purpose: This study investigates the feasibility of using complex-valued neural networks (NNs) to estimate quantitative transmit magnetic RF field (B ) maps from multi-slice localizer scans with different slice orientations in the human head at 7T, aiming to accelerate subject-specific B -calibration using parallel transmission (pTx).

Methods: Datasets containing channel-wise B -maps and corresponding multi-slice localizers were acquired in axial, sagittal, and coronal orientation in 15 healthy subjects utilizing an eight-channel pTx transceiver head coil. Training included five-fold cross-validation for four network configurations: used transversal, sagittal, coronal data, and was trained on all slice orientations.