Mesenchymal Stem/Stromal Cells Reverse Adipose Tissue Inflammation in Pigs with Metabolic Syndrome and Renovascular Hypertension.

Metabolic syndrome (MetS) is associated with low-grade inflammation, which can be exacerbated by renal artery stenosis (RAS) and renovascular hypertension, potentially worsening outcomes through pro-inflammatory cytokines. This study investigated whether mesenchymal stem/stromal cells (MSCs) could reduce fat inflammation in pigs with MetS and RAS. Twenty-four pigs were divided into Lean (control), MetS, MetS + RAS, and MetS + RAS + MSCs.

Optimizing In Vivo Data Acquisition for Robust Clinical Microvascular Imaging Using Ultrasound Localization Microscopy.

Ultrasound localization microscopy (ULM) enables microvascular imaging at spatial resolutions beyond the acoustic diffraction limit, offering significant clinical potentials. However, ULM performance relies heavily on microbubble (MB) signal sparsity, the number of detected MBs, and signal-to-noise ratio (SNR), all of which vary in clinical scenarios involving bolus MB injections. These sources of variations underscore the need to optimize MB dosage, data acquisition timing, and imaging settings in order to standardize and optimize ULM of microvasculature.

Tumor necrosis factor-stimulated gene-6 inhibits endoplasmic reticulum stress in the ischemic mouse kidney.

Kidney tissue injury in renal artery stenosis (RAS) involves inflammation, endoplasmic reticulum stress (ERS), and mitochondria damage. Tumor necrosis factor-stimulated gene-6 (TSG-6), an endogenous reparative molecule, may decrease ERS and improve renal function. To assess its impact on the stenotic murine kidney, we injected TSG-6 or vehicle for two weeks in mice with RAS.

Peripheral Endothelial Dysfunction Is Associated With Incident Major Depressive Disorder.

Background: A subset of individuals with major depressive disorder (MDD) have a high burden of cardiovascular risk factors and cerebral small-vessel disease, implicating vascular disease in the development of depression. Cross-sectional studies demonstrate a link between endothelial dysfunction and MDD, but the prospective association between peripheral endothelial dysfunction (PED) and an incident diagnosis of MDD is unknown.

Methods And Results: Patients undergoing a baseline assessment of cardiovascular risk were evaluated for PED using reactive hyperemia-peripheral arterial tonometry (≤1.

Targeted therapeutic strategies for the kidney.

Introduction: Kidney diseases impose a significant burden with high incidence and mortality rates. Current treatment options for kidney diseases are limited, necessitating urgent development of novel and effective therapeutic strategies to delay or reverse disease progression. Targeted therapies for the kidney hold promise in significantly enhancing treatment outcomes, offering hope to patients afflicted with renal disorders.

A series of cases of transthyretin amyloid cardiomyopathy with negative bone scintigraphy but a confirmed positive endomyocardial biopsy.

Background: Bone scintigraphy (BS) is established as an accurate, non-invasive method for the diagnosis of transthyretin amyloid cardiomyopathy (ATTR-CM). In a real-life setting, however, some patients with no cardiac uptake on BS turn out to have cardiac-biopsy-confirmed ATTR-CM. We retrospectively included all patients diagnosed at the French Referral Center for ATTR-CM and who had data for BS and a cardiac biopsy.

Kidney injury: the spleno-renal connection and splenic tyrosine kinase.

Kidney injury is a major medical burden and one of the most common reasons for hospitalization and poor life quality. Kidney injury can include acute kidney injury, chronic kidney disease, and immune-mediated kidney diseases most of which have no definitive therapy. The spleen is a secondary lymphoid organ in the reticuloendothelial system that plays an important role in protecting the body from various diseases.

Dyslipidemia-induced renal fibrosis related to ferroptosis and endoplasmic reticulum stress.

Dyslipidemia may induce chronic kidney disease and trigger both ferroptosis and endoplasmic reticulum (ER) stress, but the instigating factors are incompletely understood. We tested the hypothesis that different models of dyslipidemia engage distinct kidney injury mechanisms. Wild-type (WT) or proprotein-convertase subtilisin/kexin type-9 (PCSK9)-gain-of-function (GOF) Ossabaw pigs were fed with a 6-month normal diet (ND) or high-fat diet (HFD) (n = 5-6 each).

Prognostic Implications of Resistive Reserve Ratio in Patients With Nonobstructive Coronary Artery Disease With Myocardial Bridging.

Background: Myocardial bridging (MB) is accompanied by the dynamic extravascular compression of epicardial coronary arteries, leading to intracoronary hemodynamic disturbance with abnormal coronary flow profiles. We aimed to evaluate the prognostic implications of resistive reserve ratio (RRR), a composite measure of flow and pressure parameters that represents the vasodilatory capacity of the coronary arteries, in patients with angina with nonobstructive coronary artery disease (ANOCA) and MB, in comparison with coronary flow reserve (CFR).

Methods And Results: In this retrospective cohort study, we included patients with ANOCA who underwent coronary reactivity testing, where MB was identified by transient constriction in coronary artery segments between systole and diastole.

The impact of hypoxia preconditioning on mesenchymal stem cells performance in hypertensive kidney disease.

Background: Autologous mesenchymal stem cells (MSCs) have emerged as a therapeutic option for many diseases. Hypertensive kidney disease (HKD) might impair MSCs' reparative ability by altering the biomolecular properties, but the characteristics of this impairment are unclear. In our previous pre-clinical studies, we found hypoxic preconditioning (HPC) enhanced angiogenesis and suppressed senescence gene expression.

The hippocampus dissociates present from past and future goals.

Our brain adeptly navigates goals across time frames, distinguishing between urgent needs and those of the past or future. The hippocampus is a region known for supporting mental time travel and organizing information along its longitudinal axis, transitioning from detailed posterior representations to generalized anterior ones. This study investigates the role of the hippocampus in distinguishing goals over time: whether the hippocampus encodes time regardless of detail or abstraction, and whether the hippocampus preferentially activates its anterior region for temporally distant goals (past and future) and its posterior region for immediate goals.

An "out of the box" approach for prevention of ketoacidosis in youth with poorly controlled type 1 diabetes: combined use of insulin pump and long-acting insulin.

Background: Poorly controlled adolescents living with type 1 diabetes (T1D) and pump failure of insulin delivery leading to diabetic ketoacidosis (DKA) are still challenging in the western world.

Aim: To investigate the effect of a combination modality of long-acting insulin for basal coverage and a pump for boluses, on the incidence of DKA and glycemic parameters in pediatric and young adults with poorly controlled T1D.

Methods: This multicenter, observational retrospective study included 55 patients (age range 3-25 years, 52.

Renal Endothelial Single-Cell Transcriptomics Reveals Spatiotemporal Regulation and Divergent Roles of Differential Gene Transcription and Alternative Splicing in Murine Diabetic Nephropathy.

Endothelial cell (EC) injury is a crucial contributor to the progression of diabetic kidney disease (DKD), but the specific EC populations and mechanisms involved remain elusive. Kidney ECs ( = 5464) were collected at three timepoints from diabetic BTBR mice and non-diabetic littermates. Their heterogeneity, transcriptional changes, and alternative splicing during DKD progression were mapped using SmartSeq2 single-cell RNA sequencing (scRNAseq) and elucidated through pathway, network, and gene ontology enrichment analyses.

Patients With Coronary Microvascular Dysfunction Have Less Circulating α-Klotho.

Background: Coronary microvascular dysfunction (CMD) represents an early functional characteristic of coronary vascular aging. Klotho (α-klotho) is a circulating protein inversely linked to physiological aging. We examined low klotho as a potential marker for vascular aging in patients with CMD and no coronary artery disease.

Coronary Vasomotor Dysfunction Is Associated With Cardiovascular Events in Patients With Nonobstructive Coronary Artery Disease.

Background: Coronary vasomotor dysfunction (CVDys) can be comprehensively classified on the basis of anatomy and functional mechanisms.

Objectives: The aim of this study was to evaluate the association between different CVDys phenotypes and outcomes in patients with angina and nonobstructive coronary artery disease (ANOCA).

Methods: Patients with ANOCA who underwent coronary reactivity testing using an intracoronary Doppler guidewire to assess microvascular and epicardial coronary endothelium-dependent and endothelium-independent function were enrolled.

Predictive Value of Artificial Intelligence-Enabled Electrocardiography in Patients With Takotsubo Cardiomyopathy.

Background: Recent studies have indicated high rates of future major adverse cardiovascular events in patients with Takotsubo cardiomyopathy (TC), but there is no well-established tool for risk stratification. This study sought to evaluate the prognostic value of several artificial intelligence-augmented ECG (AI-ECG) algorithms in patients with TC.

Methods And Results: This study examined consecutive patients in the prospective and observational Mayo Clinic Takotsubo syndrome registry.

Whole-Body Positron Emission Tomography with F-Fluorodeoxyglucose/Magnetic Resonance Imaging as a Screening Tool for the Detection of Malignant Transformation in Individuals with Neurofibromatosis Type 1.

Malignant peripheral nerve sheath tumors (MPNSTs) are the leading cause of death in patients with neurofibromatosis type 1. They can result from premalignant neurofibromas, including neurofibromas with atypia and atypical neurofibromatous neoplasms of uncertain biologic potential. Some phenotypic characteristics have been described as associated with their development.