Variations and Asymmetry in Sacral Ventral Rami Contributions to the Bladder.

We have demonstrated in human cadavers and canines that nerve transfer to bladder vesical nerve branches is technically feasible for bladder reinnervation after nerve injury. We further clarify here that sacral (S) ventral rami contribute to these vesical branches in 36 pelvic sides (in 22 human cadavers). Gross post-mortem visualization and open anterior abdominal approaches were used, as was micro-CT of sacral nerve bundles, for further confirmation when needed.

Repetitive Overuse Injury Causes Entheseal Damage and Palmar Muscle Fibrosis in Older Rats.

Overuse injury is a frequent diagnosis in occupational medicine and athletics. Using an established model of upper extremity overuse, we sought to characterize changes occurring in the forepaws and forelimbs of mature female rats (14-18 months of age). Thirty-three rats underwent a 4-week shaping period, before performing a high-repetition low-force (HRLF) task for 12 weeks, with the results being compared to 32 mature controls.

Evaluating sex-specific responses to western diet across the lifespan: impact on cardiac function and transcriptomic signatures in C57BL/6J mice at 530 and 640/750 days of age.

Background: Long-term consumption of Western Diet (WD) is a well-established risk factor for the development of cardiovascular disease (CVD); however, there is a paucity of studies on the long-term effects of WD on the pathophysiology of CVD and sex-specific responses.

Methods: Our study aimed to investigate the sex-specific pathophysiological changes in left ventricular (LV) function using transthoracic echocardiography (ECHO) and LV tissue transcriptomics in WD-fed C57BL/6 J mice for 125 days, starting at the age of 300 through 425 days.

Results: In female mice, consumption of the WD diet showed long-term effects on LV structure and possible development of HFpEF-like phenotype with compensatory cardiac structural changes later in life.

Quantitative Real-Time PCR for Circular RNA Detection and Analysis.

In eukaryotes, nearly 2% of the genome represented by the coding proteins. However, emerging evidence suggest more than 75% of the human genome referred to as noncoding part also plays a crucial role in governing major regulatory pathways. Noncoding RNAs can be categorized into several groups, such as microRNAs (miRNAs), small nuclear RNA (snRNAs), small nucleolar RNA (snoRNAs), transfer RNA (tRNA), and circular RNA (circRNAs), which contribute to this regulatory landscape.

Evaluating massage therapy for radiation-induced fibrosis in rats: preliminary findings and palpation results.

Radiation-induced fibrosis (RIF) is a common side effect of cancer treatment, but can manifest into a devastating syndrome for which there is no preventive measure or cure. In rats who perform a repetitive work task, who left untreated develop signs and symptoms that resemble repetitive motion disorders in humans, we have shown that manual therapy prevents the development of fibrosis and other key biomarkers. The fibrosis of RIF and repetitive motion disorders has similar biomarkers.

Effectiveness of low-fat diet on the levels of insulin-like growth factor-1 and insulin-like growth factor binding proteins: a systematic review and meta-analysis of randomized controlled clinical trials.

Background: Previous researches on the effect of low-fat diet (LF) on insulin-like growth factor-1 (IGF-1), and its binding proteins (IGFBPs) did not reach a consensus result, and there is no study summarizing these findings. Thus, this systematic review and meta-analysis of randomized control trials (RCTs) was performed to pool available evidence and answer the question whether dietary fat can affect IGF-1 and IGFBPs or not.

Methods: PubMed, Scopus, ISI Web of Science, Google, Google scholar, ProQuest, and the Cochrane Library were searched without language restrictions until July 2, 2024 to retrieve related studies.

Early movement restriction impairs the development of sensorimotor integration, motor skills and memory in rats: Towards a preclinical model of developmental coordination disorder?

Children with neurodevelopmental disorders, such as developmental coordination disorder (DCD), exhibit gross to fine sensorimotor impairments, reduced physical activity and interactions with the environment and people. This disorder co-exists with cognitive deficits, executive dysfunctions and learning impairments. Previously, we demonstrated in rats that limited amounts and atypical patterns of movements and somatosensory feedback during early movement restriction manifested in adulthood as degraded postural and locomotor abilities, and musculoskeletal histopathology, including muscle atrophy, hyperexcitability within sensorimotor circuitry and maladaptive cortical plasticity, leading to functional disorganization of the primary somatosensory and motor cortices in the absence of cortical histopathology.

Integrated systems biology identifies disruptions in mitochondrial function and metabolism as key contributors to heart failure with preserved ejection fraction (HFpEF).

Background: Heart failure with preserved ejection fraction (HFpEF) accounts for ~50% of HF cases, with no effective treatments. The ZSF1-obese rat model recapitulates numerous clinical features of HFpEF including hypertension, obesity, metabolic syndrome, exercise intolerance, and LV diastolic dysfunction. Here, we utilized a systems-biology approach to define the early metabolic and transcriptional signatures to gain mechanistic insight into the pathways contributing to HFpEF development.

Integrated manual therapies: IASP taskforce viewpoint.

Introduction: Manual therapy refers to a range of hands-on interventions used by various clinical professionals, such as osteopaths, osteopathic physicians, chiropractors, massage therapists, physiotherapists, and physical therapists, to treat patients experiencing pain.

Objectives: To present existing evidence of mechanisms and clinical effectiveness of manual therapy in pain.

Methods: This Clinical Update focuses on the 2023 International Association for the Study of Pain Global Year for Integrative Pain Care.

Bempedoic acid suppresses diet-induced hepatic steatosis independently of ATP-citrate lyase.

ATP citrate lyase (ACLY) synthesizes acetyl-CoA for de novo lipogenesis (DNL), which is elevated in metabolic dysfunction-associated steatotic liver disease. Hepatic ACLY is inhibited by the LDL-cholesterol-lowering drug bempedoic acid (BPA), which also improves steatosis in mice. While BPA potently suppresses hepatic DNL and increases fat catabolism, it is unclear if ACLY is its primary molecular target in reducing liver triglyceride.

A neuro-lymphatic communication guides lymphatic development by CXCL12 and CXCR4 signaling.

Lymphatic vessels grow through active sprouting and mature into a vascular complex that includes lymphatic capillaries and collecting vessels that ensure fluid transport. However, the signaling cues that direct lymphatic sprouting and patterning remain unclear. In this study, we demonstrate that chemokine signaling, specifically through CXCL12 and CXCR4, plays crucial roles in regulating lymphatic development.

Transcriptome wide changes in long noncoding RNAs in diabetic ischemic heart disease.

More than 10% of adults in the United States have type 2 diabetes mellitus (DM) with a 2-4 times higher prevalence of ischemic heart disease than the non-diabetics. Despite extensive research approaches to limit this life-threatening condition have proven unsuccessful, highlighting the need for understanding underlying molecular mechanisms. Long noncoding RNAs (lncRNAs), which regulate gene expression by acting as signals, decoys, guides, or scaffolds have been implicated in diverse cardiovascular conditions.

Brown fat ATP-citrate lyase links carbohydrate availability to thermogenesis and guards against metabolic stress.

Brown adipose tissue (BAT) engages futile fatty acid synthesis-oxidation cycling, the purpose of which has remained elusive. Here, we show that ATP-citrate lyase (ACLY), which generates acetyl-CoA for fatty acid synthesis, promotes thermogenesis by mitigating metabolic stress. Without ACLY, BAT overloads the tricarboxylic acid cycle, activates the integrated stress response (ISR) and suppresses thermogenesis.

Adrenergic orchestration of immune cell dynamics in response to cardiac stress.

Immune cells contribute approximately 5-10 % of the heart's total cell population, including several myeloid cell and lymphocyte cell subsets, which, despite their relatively small percentages, play important roles in cardiac homeostasis and remodeling responses to various forms of injury and long-term stress. Pathological cardiac stress activates the sympathetic nervous system (SNS), resulting in the release of the catecholamines epinephrine and norepinephrine either systemically or from sympathetic nerve terminals within various lymphoid organs. Acting at α- or β-adrenergic receptors (αAR, βAR), catecholamines regulate immune cell hematopoiesis, egress and migration in response to stress.

Loss of cardiomyocyte-specific adhesion G-protein-coupled receptor G1 (ADGRG1/GPR56) promotes pressure overload-induced heart failure.

Adhesion G-protein-coupled receptors (AGPCRs), containing large N-terminal ligand-binding domains for environmental mechano-sensing, have been increasingly recognized to play important roles in numerous physiologic and pathologic processes. However, their impact on the heart, which undergoes dynamic mechanical alterations in healthy and failing states, remains understudied. ADGRG1 (formerly known as GPR56) is widely expressed, including in skeletal muscle where it was previously shown to mediate mechanical overload-induced muscle hypertrophy; thus, we hypothesized that it could impact the development of cardiac dysfunction and remodeling in response to pressure overload.

Nuclear ATP-citrate lyase regulates chromatin-dependent activation and maintenance of the myofibroblast gene program.

Differentiation of cardiac fibroblasts to myofibroblasts is necessary for matrix remodeling and fibrosis in heart failure. We previously reported that mitochondrial calcium signaling drives α-ketoglutarate-dependent histone demethylation, promoting myofibroblast formation. Here we investigate the role of ATP-citrate lyase (ACLY), a key enzyme for acetyl-CoA biosynthesis, in histone acetylation regulating myofibroblast fate and persistence in cardiac fibrosis.

Mitochondrial calcium uniporter channel gatekeeping in cardiovascular disease.

The mitochondrial calcium (Ca) uniporter channel (mtCU) resides at the inner mitochondrial membrane and is required for Ca to enter the mitochondrial matrix. The mtCU is essential for cellular function, as Ca regulates metabolism, bioenergetics, signaling pathways and cell death. Ca uptake is primarily regulated by the MICU family (MICU1, MICU2, MICU3), EF-hand-containing Ca-sensing proteins, which respond to cytosolic Ca concentrations to modulate mtCU activity.

MICU1 and MICU2 control mitochondrial calcium signaling in the mammalian heart.

Activating Ca-sensitive enzymes of oxidative metabolism while preventing calcium overload that leads to mitochondrial and cellular injury requires dynamic control of mitochondrial Ca uptake. This is ensured by the mitochondrial calcium uptake (MICU)1/2 proteins that gate the pore of the mitochondrial calcium uniporter (mtCU). MICU1 is relatively sparse in the heart, and recent studies claimed the mammalian heart lacks MICU1 gating of mtCU.

Lipids associated with atherosclerotic plaque instability revealed by mass spectrometry imaging of human carotid arteries.

Background And Aims: Lipids constitute one of the main components of atherosclerosis lesions and are the mediators of many mechanisms involved in plaque progression and stability. Here we tested the hypothesis that lipids known to be involved in plaque development exhibited associations with plaque vulnerability. We used spatial lipidomics to overcome plaque heterogeneity and to compare lipids from specific regions of symptomatic and asymptomatic human carotid atherosclerotic plaques.

Integrated single-cell RNA-seq analysis reveals mitochondrial calcium signaling as a modulator of endothelial-to-mesenchymal transition.

Endothelial cells (ECs) are highly plastic, capable of differentiating into various cell types. Endothelial-to-mesenchymal transition (EndMT) is crucial during embryonic development and contributes substantially to vascular dysfunction in many cardiovascular diseases (CVDs). While targeting EndMT holds therapeutic promise, understanding its mechanisms and modulating its pathways remain challenging.

Cardiac Progenitor Cell Metabolism.

Metabolism has emerged recently as an important determinant of stem cell function. Changes in metabolic signaling pathways precede changes in stem cell molecular and functional response. Pluripotent stem cells are highly proliferative and known to exhibit increased glycolysis.

SGLT2 inhibitors activate pantothenate kinase in the human heart.

Inhibitors of sodium glucose cotransporter-2 (SGLT2i) demonstrate strong symptomatic and mortality benefits in the treatment of heart failure but appear to do so independently of SGLT2. The relevant pharmacologic target of SGLT2i remains unclear. We show here that SGLT2i directly activate pantothenate kinase 1 (PANK1), the rate-limiting enzyme that initiates the conversion of pantothenate (vitamin B5) to coenzyme-A (CoA), an obligate co-factor for all major pathways of fuel use in the heart.

A Retinoic Acid:YAP1 signaling axis controls atrial lineage commitment.

Vitamin A/Retinoic Acid (Vit A/RA) signaling is essential for heart development. In cardiac progenitor cells (CPCs), RA signaling induces the expression of atrial lineage genes while repressing ventricular genes, thereby promoting the acquisition of an atrial cardiomyocyte cell fate. To achieve this, RA coordinates a complex regulatory network of downstream effectors that is not fully identified.