intracellular metabolism

BACKGROUND: Activation of the vagus nerve mediates cardioprotection and attenuates myocardial ischemia/reperfusion (I/R) injury. In response to vagal activation, acetylcholine (ACh) is released from the intracardiac nervous system (ICNS) and activates intracellular cardioprotective signaling cascades. Recently, however, a non-neuronal cholinergic cardiac system (NNCCS) in cardiomyocytes has been described as an additional source of ACh. AIM: To investigate whether the NNCCS mediates cardioprotection in absence of vagal and ICNS activation...

The mammalian cytosolic sulfotransferases (SULTs) catalyze the sulfation of endocrine hormones as well as a broad array of drugs, environmental chemicals, and other xenobiotics. Many endocrine-disrupting chemicals (EDCs) interact with these SULTs as substrates and inhibitors, and thereby alter sulfation reactions responsible for metabolism and regulation of endocrine hormones such as estrogens and thyroid hormones. EDCs or their metabolites may also regulate expression of SULTs through direct interaction with nuclear receptors and other transcription factors...

AIM: To investigate the effects of adenosine kinase (ADK), a key enzyme in determining intracellular adenosine levels, on β cells, and their underlying mechanism. METHODS: Genetic animal models and transgenic immortalized cells were applied to study the effect of ADK on islet beta-cell proliferation and function. The beta-cell mass and response to glucose were measured in vivo using mice with beta-cell-specific ADK overexpression, and in vitro using ADK-overexpressed immortalized beta-cell...

BACKGROUND: Targeting ferroptosis has been identified as a promising approach for the development of cancer therapies. Monounsaturated fatty acid (MUFA) is a type of lipid that plays a crucial role in inhibiting ferroptosis. Ficolin 3 (FCN3) is a component of the complement system, serving as a recognition molecule against pathogens in the lectin pathway. Recent studies have reported that FCN3 demonstrates inhibitory effects on the progression of certain tumors. However, whether FCN3 can modulate lipid metabolism and ferroptosis remains largely unknown...

The physiological efficiency of cells largely depends on the possibility of metabolic adaptations to changing conditions, especially on the availability of nutrients. Central carbon metabolism has an essential role in cellular function. In most cells is based on glucose, which is the primary energy source, provides the carbon skeleton for the biosynthesis of important cell macromolecules, and acts as a signalling molecule. The metabolic flux between pathways of carbon metabolism such as glycolysis, pentose phosphate pathway, and mitochondrial oxidative phosphorylation is dynamically adjusted by specific cellular economics responding to extracellular conditions and intracellular demands...

Human pluripotent stem cell-derived β cells (hPSC-β cells) show the potential to restore euglycemia. However, the immature functionality of hPSC-β cells has limited their efficacy in application. Here, by deciphering the continuous maturation process of hPSC-β cells post transplantation via single-cell RNA sequencing (scRNA-seq) and single-cell assay for transposase-accessible chromatin sequencing (scATAC-seq), we show that functional maturation of hPSC-β cells is an orderly multistep process during which cells sequentially undergo metabolic adaption, removal of negative regulators of cell function, and establishment of a more specialized transcriptome and epigenome...

α,α-trehalose is a well-known sugar that plays a key role in establishing tolerance to environmental stresses in many organisms, except unicellular eukaryotes. However, almost nothing is known about α,β-trehalose, including their synthesis, function, and even presence in living organisms. In this study, we identified α,β-trehalose in the resting cyst, a dormancy cell form characterized by extreme tolerance to environmental stresses, of the ciliated protist Colpoda cucullus, using high-performance liquid chromatography (HPLC), and a proton nuclear magnetic resonance (1 H NMR)...

microRNAs (miRNAs), a class of non-coding RNA with 20-24 nucleotides, are defined as the powerful regulators for gene expression. miR-21 is a multifunctional miRNA enriched in the circulatory system and multiple organs, which not only serves as a non-invasive biomarker in disease diagnosis, but also participates in many cellular activities. In various chronic liver diseases, the increase of miR-21 affects glycolipid metabolism, viral infection, inflammatory and immune cell activation, hepatic stellate cells activation and tissue fibrosis, and autophagy...

Aims: the study aimed to (i) use adeno-associated virus technology to modulate parvalbumin (PV) gene expression, both through overexpression and silencing, within the hippocampus of male mice and (ii) assess the impact of PV on the metabolic pathway of glutamate and γ-aminobutyric acid (GABA). Methods: a status epilepticus (SE) mouse model was established by injecting kainic acid into the hippocampus of transgenic mice. When the seizures of mice reached SE, the mice were killed at that time point and 30 min after the onset of SE...

BACKGROUND: Acute kidney injury (AKI) is a common and severe complication in patients treated at an Intensive Care Unit (ICU). The pathogenesis of AKI has been reported to involve hypoperfusion, diminished oxygenation, systemic inflammation, and damage by increased intracellular iron concentration. Hepcidin, a regulator of iron metabolism, has been shown to be associated with sepsis and septic shock, conditions that can result in AKI. Heparin binding protein (HBP) has been reported to be associated with sepsis and AKI...

BACKGROUND: Transarterial chemoembolization is the first-line treatment for intermediate-stage HCC. However, the response rate to transarterial chemoembolization varies, and the molecular mechanisms underlying variable responses are poorly understood. Patient-derived hepatocellular carcinoma organoids (HCCOs) offer a novel platform to investigate the molecular mechanisms underlying doxorubicin resistance. METHODS: We evaluated the effects of hypoxia and doxorubicin on cell viability and cell cycle distribution in 20 patient-derived HCCO lines...

A canonical view of the primary physiological function of myoglobin (Mb) is that it is an oxygen (O2 ) storage protein supporting mitochondrial oxidative phosphorylation, especially as the tissue O2 partial pressure ( p O2 ) drops and Mb offloads O2 . Besides O2 storage/transport, recent findings support functions for Mb in lipid trafficking and sequestration, interacting with cellular glycolytic metabolites such as lactate (LAC) and pyruvate (PYR) , and "ectopic" expression in some types of cancer cells and in brown adipose tissue (BAT)...

The Rab small GTPases are characterized by the distinct intracellular localization and modulate various endocytic, transcytic and exocytic transport pathways. Rab proteins function as scaffolds that connect signaling pathways and intracellular membrane trafficking processes through the recruitment of effectors, such as tethering factors, phosphatases, motors and kinases. In different cancers, Rabs play as either an onco-protein or a tumor suppressor role, highly dependending on the context. The molecular mechanistic research has revealed that Rab proteins are involved in cancer progression through influences on migration, invasion, metabolism, exosome secretion, autophagy, and drug resistance of cancer cells...

Ferroptosis is a newly discovered form of programmed cell death triggered by intracellular iron overload, which leads to the accumulation of lipid peroxides in various cells. It has been implicated in the pathogenesis and progression of various diseases, including tumors, neurological disorders, and cardiovascular diseases. The intricate mechanism underlying ferroptosis involves an imbalance between the oxidation and antioxidant systems, disturbances in iron metabolism, membrane lipid peroxidation, and dysregulation of amino acid metabolism...

Mycobacterium tuberculosis causes tuberculosis (TB), one of the world's most deadly infections. Lipids play an important role in M. tuberculosis pathogenesis. M. tuberculosis grows intracellularly within lipid-laden macrophages and extracellularly within the cholesterol-rich caseum of necrotic granulomas and pulmonary cavities. Evolved from soil saprophytes that are able to metabolize cholesterol from organic matter in the environment, M. tuberculosis inherited an extensive and highly conserved machinery to metabolize cholesterol...

With the aging global population, type 2 diabetes mellitus (T2DM) and osteoporosis(OP) are becoming increasingly prevalent. Diabetic osteoporosis (DOP) is a metabolic bone disorder characterized by abnormal bone tissue structure and reduced bone strength in patients with diabetes. Studies have revealed a close association among diabetes, increased fracture risk, and disturbances in iron metabolism. This review explores the concept of ferroptosis, a non-apoptotic cell death process dependent on intracellular iron, focusing on its role in DOP...

CD8+ cytotoxic T lymphocytes (CTLs) are central mediators of tumor immunity and immunotherapies. Upon tumor antigen recognition, CTLs differentiate from naive/memory-like toward terminally exhausted populations with more limited function against tumors. Such differentiation is regulated by both immune signals, including T cell receptors (TCRs), co-stimulation, and cytokines, and metabolism-associated processes. These immune signals shape the metabolic landscape via signaling, transcriptional and post-transcriptional mechanisms, while metabolic processes in turn exert spatiotemporal effects to modulate the strength and duration of immune signaling...

Mitochondria are semiautonomous organelles with diverse metabolic and cellular functions including anabolism and energy production through oxidative phosphorylation. Following the pioneering observations of Otto Warburg nearly a century ago, an immense body of work has examined the role of mitochondria in cancer pathogenesis and progression. Here, we summarize the current state of the field, which has coalesced around the position that functional mitochondria are required for cancer cell proliferation. In this review, we discuss how mitochondria influence tumorigenesis by impacting anabolism, intracellular signaling, and the tumor microenvironment...

Recent studies revealed that mitochondria are not only a place of vitamin D3 metabolism but also direct or indirect targets of its activities. This review summarizes current knowledge on the regulation of ion channels from plasma and mitochondrial membranes by the active form of vitamin D3 (1,25(OH)2 D3 ). 1,25(OH)2 D3 , is a naturally occurring hormone with pleiotropic activities; implicated in the modulation of cell differentiation, and proliferation and in the prevention of various diseases, including cancer...

The urgent need for antimicrobial agents to combat infections caused by multidrug-resistant bacteria facilitates the exploration of alternative strategies such as photosensitizer (PS)-mediated photoinactivation. However, increasing studies have discovered uncorrelated bactericidal activities among PSs possessing similar photodynamic and pathogen-targeted properties. To optimize the photodynamic therapy (PDT) against infections, we investigated three type-I PSs of D-π-A AIEgens TI, TBI, and TTI. The capacities of reactive oxygen species (ROS) generation of TI, TBI, and TTI did not align with their bactericidal activities...