Reevaluating Anti-Inflammatory Therapy: Targeting Senescence to Balance Anti-Cancer Efficacy and Vascular Disease.

Modulating immune function is a critical strategy in cancer and atherosclerosis treatments. For cancer, boosting or maintaining the immune system is crucial to prevent tumor growth. However, in vascular disease, mitigating immune responses can decrease inflammation and slow atherosclerosis progression.

Energy metabolism in osteoprogenitors and osteoblasts: Role of the pentose phosphate pathway.

Bioenergetic preferences of osteolineage cells, including osteoprogenitors and osteoblasts (OBs), are a matter of intense debate. Early studies pointed to OB reliance on glucose and aerobic glycolysis while more recent works indicated the importance of glutamine as a mitochondrial fuel. Aiming to clarify this issue, we performed metabolic tracing of C-labeled glucose and glutamine in human osteolineage cells: bone marrow stromal (a.

PPARγ drives mitochondrial stress signaling and the loss of atrial cardiomyocytes in newborn mice exposed to hyperoxia.

Diastolic dysfunction is increasingly common in preterm infants exposed to supplemental oxygen (hyperoxia). Previous studies in neonatal mice showed hyperoxia suppresses fatty acid synthesis genes required for proliferation and survival of atrial cardiomyocytes. The loss of atrial cardiomyocytes creates a hypoplastic left atrium that inappropriately fills the left ventricle during diastole.

A kidney-hypothalamus axis promotes compensatory glucose production in response to glycosuria.

The kidneys facilitate energy conservation through reabsorption of nutrients including glucose. Almost all the filtered blood glucose is reabsorbed by the kidneys. Loss of glucose in urine (glycosuria) is offset by an increase in endogenous glucose production to maintain normal energy supply in the body.

Manipulating mitochondrial pyruvate carrier function causes metabolic remodeling in corneal myofibroblasts that ameliorates fibrosis.

Myofibroblasts are key cellular effectors of corneal wound healing from trauma, surgery, or infection. However, their persistent deposition of disorganized extracellular matrix can also cause corneal fibrosis and visual impairment. Recent work showed that the PPARγ agonist Troglitazone can mitigate established corneal fibrosis, and parallel in vitro data suggested this occurred through inhibition of the mitochondrial pyruvate carrier (MPC) rather than PPARγ.

Cardiac transplant rejection assessment with 18F-FDG PET-CT: initial single-centre experience for diagnosis and management.

Background: Rejection is a major cause of mortality and morbidity in heart transplant (HTx) recipients. Current methods for diagnosing rejection have limitations. Imaging methods to map the entire left ventricle and reliably identify potential sites of rejection is lacking.

Reactive oxygen species generation by reverse electron transfer at mitochondrial complex I under simulated early reperfusion conditions.

Ischemic tissues accumulate succinate, which is rapidly oxidized upon reperfusion, driving a burst of mitochondrial reactive oxygen species (ROS) generation that triggers cell death. In isolated mitochondria with succinate as the sole metabolic substrate under non-phosphorylating conditions, 90 % of ROS generation is from reverse electron transfer (RET) at the Q site of respiratory complex I (Cx-I). Together, these observations suggest Cx-I RET is the source of pathologic ROS in reperfusion injury.

Metallic micronutrients are associated with the structure and function of the soil microbiome.

The relationship between metallic micronutrients and soil microorganisms, and thereby soil functioning, has been little explored. Here, we investigate the relationship between metallic micronutrients (Fe, Mn, Cu, Zn, Mo and Ni) and the abundance, diversity and function of soil microbiomes. In a survey across 180 sites in China, covering a wide range of soil conditions the structure and function of the soil microbiome are highly correlated with metallic micronutrients, especially Fe, followed by Mn, Cu and Zn.

Reactive Oxygen Species Generation by Reverse Electron Transfer at Mitochondrial Complex I Under Simulated Early Reperfusion Conditions.

Ischemic tissues accumulate succinate, which is rapidly oxidized upon reperfusion, driving a burst of mitochondrial reactive oxygen species (ROS) generation that triggers cell death. In isolated mitochondria with succinate as the sole metabolic substrate under non-phosphorylating conditions, 90% of ROS generation is from reverse electron transfer (RET) at the Q site of respiratory complex I (Cx-I). Together, these observations suggest Cx-I RET is the source of pathologic ROS in reperfusion injury.

Novel Roles for the Transcriptional Repressor E4BP4 in Both Cardiac Physiology and Pathophysiology.

Circadian clocks temporally orchestrate biological processes critical for cellular/organ function. For example, the cardiomyocyte circadian clock modulates cardiac metabolism, signaling, and electrophysiology over the course of the day, such that, disruption of the clock leads to age-onset cardiomyopathy (through unknown mechanisms). Here, we report that genetic disruption of the cardiomyocyte clock results in chronic induction of the transcriptional repressor E4BP4.

A kidney-hypothalamus axis promotes compensatory glucose production in response to glycosuria.

The kidneys facilitate energy conservation through reabsorption of nutrients including glucose. Almost all the filtered blood glucose is reabsorbed by the kidneys. Loss of glucose in urine (glycosuria) is offset by an increase in endogenous glucose production to maintain normal energy supply in the body.

Role of the Mitochondrial Permeability Transition in Bone Metabolism and Aging.

The mitochondrial permeability transition pore (MPTP) and its positive regulator, cyclophilin D (CypD), play important pathophysiological roles in aging. In bone tissue, higher CypD expression and pore activity are found in aging; however, a causal relationship between CypD/MPTP and bone degeneration needs to be established. We previously reported that CypD expression and MPTP activity are downregulated during osteoblast (OB) differentiation and that manipulations in CypD expression affect OB differentiation and function.

Donor specific antibodies association with survival and adverse events after heart transplantation: A single center retrospective study between 2006 and 2021.

Objective: Newly detected donor HLA-specific antibodies (DSA) are historically known to be associated with reduced survival in heart transplant patients. Our objective is to clarify the modern incidence of DSA and determine its relationship with survival and MACE.

Methods: This retrospective study included all patients undergoing orthotopic heart transplantation at Harefield Hospital, London between January 1, 2006 and May 31, 2021.

Distinct effects of intracellular vs. extracellular acidic pH on the cardiac metabolome during ischemia and reperfusion.

Tissue ischemia results in intracellular pH (pH) acidification, and while metabolism is a known driver of acidic pH, less is known about how acidic pH regulates metabolism. Furthermore, acidic extracellular (pH) during early reperfusion confers cardioprotection, but how this impacts metabolism is unclear. Herein we employed LCMS based targeted metabolomics to analyze perfused mouse hearts exposed to: (i) control perfusion, (ii) hypoxia, (iii) ischemia, (iv) enforced acidic pH, (v) control reperfusion, and (vi) acidic pH (6.

Biodiesel Co-Product enhances microbial stability and beneficial microbial communities along a gradient of soil water content.

Biodiesel Co-Product (BCP) is a complex carbonaceous liquid formed during the commercial production of biodiesel. Previously, BCP was shown to decrease nitrogen (N) leaching from the soil, but the effects of BCP on the diversity, composition, and structure of soil microbial communities are not well understood. Here, we applied 1.

Dysregulation of Bile Acids, Lipids, and Nucleotides in Psoriatic Arthritis Revealed by Unbiased Profiling of Serum Metabolites.

Objective: The transition from psoriasis to psoriatic arthritis (PsA) occurs in 20-30% of patients; however, the mechanisms underlying the emergence of musculoskeletal disease are not well understood. Metabolic disease is prevalent in psoriasis patients, but whether metabolic factors, other than obesity, increase arthritis risk in psoriasis patients is not known. This study was undertaken to investigate the link between metabolic changes and disease progression in psoriasis patients.

Inhibiting Succinate Release Worsens Cardiac Reperfusion Injury by Enhancing Mitochondrial Reactive Oxygen Species Generation.

Background The metabolite succinate accumulates during cardiac ischemia. Within 5 minutes of reperfusion, succinate returns to baseline levels via both its release from cells and oxidation by mitochondrial complex II. The latter drives reactive oxygen species (ROS) generation and subsequent opening of the mitochondrial permeability transition (PT) pore, leading to cell death.

Peripheral blood mononuclear cell gene expression and cytokine profiling in patients with intermittent claudication who exhibit exercise induced acute renal injury.

Background: Intermittent claudication (IC) is a common manifestation of peripheral arterial disease. Some patients with IC experience a rise in Urinary N-acetyl-β-D-Glucosaminidase (NAG)/ Creatinine (Cr) ratio, a marker of renal injury, following exercise. In this study, we aim to investigate whether peripheral blood mononuclear cells (PBMC) from patients with IC who exhibit a rise in urinary NAG/ Cr ratio following exercise exhibit differential IL-10/ IL-12 ratio and gene expression compared to those who do not have a rise in NAG/ Cr ratio.

Comparison of the clinical sensitivity and specificity of two commercial RNA SARS-CoV-2 assays.

Objectives: This study aimed to compare the performance of the NeuMoDx™ SARS-CoV-2 Assay, implemented on the NeuMoDx 96 Molecular System, with that of the ThermoFisher TaqPath™ COVID-19 CE-IVD RT-PCR Kit (reference method).

Methods: Overall, 450 nasopharyngeal swab samples, previously tested using the reference method, were tested by the NeuMoDx Assay, and the clinical sensitivity and specificity of the assay were analyzed.

Results: By retrospective statistical analysis of all valid results, the NeuMoDx Assay had a clinical specificity of 100% (95% confidence interval [CI]: 98.

Three source-partitioning of CO fluxes based on a dual-isotope approach to investigate interactions between soil organic carbon, glucose and straw.

Inputs of available organic materials into soil alter the decomposition of soil organic matter (SOM), a process called priming effect. Organic carbon (C) inputs in terrestrial ecosystems are common from various sources (e.g.

Nucleus-mitochondria positive feedback loop formed by ERK5 S496 phosphorylation-mediated poly (ADP-ribose) polymerase activation provokes persistent pro-inflammatory senescent phenotype and accelerates coronary atherosclerosis after chemo-radiation.

The incidence of cardiovascular disease (CVD) is higher in cancer survivors than in the general population. Several cancer treatments are recognized as risk factors for CVD, but specific therapies are unavailable. Many cancer treatments activate shared signaling events, which reprogram myeloid cells (MCs) towards persistent senescence-associated secretory phenotype (SASP) and consequently CVD, but the exact mechanisms remain unclear.

BSHI/BTS guidance on crossmatching before deceased donor kidney transplantation.

All UK H&I laboratories and transplant units operate under a single national kidney offering policy, but there have been variations in approach regarding when to undertake the pre-transplant crossmatch test. In order to minimize cold ischaemia times for deceased donor kidney transplantation we sought to find ways to be able to report a crossmatch result as early as possible in the donation process. A panel of experts in transplant surgery, nephrology, specialist nursing in organ donation and H&I (all relevant UK laboratories represented) assessed evidence and opinion concerning five factors that relate to the effectiveness of the crossmatch process, as follows: when the result should be ready for reporting; what level of donor HLA typing is needed; crossmatch sample type and availability; fairness and equity; risks and patient safety.