• MitoTempo
• Mitochondrial defects
• Neurodegeneration
• Neuroprotection
• Nε-carboxymethyl lysine

• Humans
• Lysine/analogs & derivatives
• Lysine/metabolism
• Mitochondria/metabolism
• Mitochondria/pathology
• Mitochondria/drug effects
• Neurons/metabolism
• Neurons/pathology
• Neurons/drug effects
• Reactive Oxygen Species/metabolism
• Organophosphorus Compounds/pharmacology
• Endoplasmic Reticulum Stress/drug effects
• Membrane Potential, Mitochondrial/drug effects
• Cell Line, Tumor
• Cell Survival/drug effects
• Glycation End Products, Advanced/metabolism
• Homeostasis
• Antioxidants/pharmacology
• Antioxidants/metabolism
• Neuroblastoma/pathology
• Neuroblastoma/metabolism
• Piperidines

• NOX4
• air pollution
• particulate matter (PM)
• reactive oxygen species (ROS)
• voltage-dependent anion-selective channel 1 (VDAC1)

• Particulate Matter/toxicity
• NADPH Oxidase 4/metabolism
• NADPH Oxidase 4/genetics
• Reactive Oxygen Species/metabolism
• Apoptosis/drug effects
• Humans
• Mitochondria/metabolism
• Mitochondria/drug effects
• Neurons/metabolism
• Neurons/drug effects
• Neurons/pathology
• Cell Line, Tumor
• Oxidative Stress/drug effects
• Animals
• Mice
• NADPH Oxidase 2/metabolism
• NADPH Oxidase 2/genetics

• NRF-2017R1A5A2015369 National Research Foundation of Korea
• NRF-2020R1I1A1A01070465 National Research Foundation of Korea
• NRF-2019R1A2C1084880 National Research Foundation of Korea
• NRF-2022R1A2C2011079 National Research Foundation of Korea
• NRF-2022R1C1C2009853 National Research Foundation of Korea

• Albumin
• Cardiac arrest
• Emergency department
• OHCA
• Phosphorus
• Prognosis

• Adult
• Humans
• Prognosis
• Cardiopulmonary Resuscitation
• Out-of-Hospital Cardiac Arrest
• Phosphates
• Albumins

• MCF-7
• MDA-MB-231
• acid phosphatase
• ecto-phosphatase activity
• inorganic phosphate

• Humans
• Female
• Hydrogen Peroxide/pharmacology
• Phosphates/pharmacology
• Phosphates/metabolism
• Breast Neoplasms
• Phosphoric Monoester Hydrolases
• Hydrolysis
• Tumor Microenvironment

• 0012017 Coordenação de Aperfeiçoamento de Pessoal de Nível Superior
• 401134/2014-8 Conselho Nacional de Desenvolvimento Científico e Tecnológico
• e-26/201.300/2014 Fundação Carlos Chagas Filho de Amparo à Pesquisa do Estado do Rio de Janeiro

• cell biology
• energy metabolism
• inorganic polyphosphate
• mitochondria
• mitochondrial physiology
• polyP

• Animals
• Energy Metabolism
• Mammals/metabolism
• Mitochondria/metabolism
• Mitochondrial Permeability Transition Pore/metabolism
• Polymers
• Polyphosphates/metabolism

• R00 AG055701 NIA NIH HHS

• Chronic Kidney Disease
• Ferritin H
• HIF-1α
• Nrf2
• Phosphorus
• Vascular calcification
• iron

• Humans
• Rats
• Animals
• Iron/metabolism
• Phosphorus
• NF-E2-Related Factor 2/metabolism
• Renal Insufficiency, Chronic/drug therapy
• Renal Insufficiency, Chronic/complications
• Ferritins
• Calcium/metabolism
• Vascular Calcification/drug therapy
• Vascular Calcification/etiology
• Cardiovascular Diseases/complications
• RNA, Messenger

• stem-cell differentiation
• cell division

• Humans
• Osteogenesis
• Genes, cdc
• Glycerophosphates/pharmacology
• Cell Line

• Engineering and Physical Sciences Research Council

• FCAVD
• apoptosis
• calcification
• electrochemical impedance spectroscopy (EIS)
• extracellular matrix (ECM)

• Leipzig University
• German Research Foundation

• All-cause death
• Cardiocerebrovascular death
• Maintenance hemodialysis
• Phosphate reduction rate

• gzwkj2021- 081 Science and Technology Foundation of Guizhou Provincial Health Commission

• diabetes
• hypertension
• insulin
• obesity
• phosphate burden

• Humans
• Metabolic Syndrome/etiology
• Phosphates/metabolism
• Insulin/metabolism
• Cardiovascular Diseases
• Phosphorus

Regular intake of ready-to-eat meals is related to obesity and several noninfectious illnesses, such as cardiovascular diseases, hypertension, diabetes mellitus (DM), and tumors. Processed foods contain high calories and are often enhanced with excess refined sugar, saturated and trans fat, Na⁺ andphosphate-containing taste enhancers, and preservatives. Studies showed that monosodium glutamate (MSG) induces raised echelons of oxidative stress, and excessive hepatic lipogenesis is concomitant to obesity and type 2 diabetes mellitus (T2DM). Likewise, more than standard salt intake adversely affects the cardiovascular system, renal system, and central nervous system (CNS), especially the brain. Globally, excessive utilization of phosphate-containing preservatives and additives contributes unswervingly to excessive phosphate intake through food. In addition, communities and even health experts, including medical doctors, are not well-informed about the adverse effects of phosphate preservatives on human health. Dietary phosphate excess often leads to phosphate toxicity, ultimately potentiating kidney disease development. The mechanisms involved in phosphate-related adverse effects are not explainable. Study reports suggested that high blood level of phosphate causes vascular ossification through the deposition of Ca²⁺ and substantially alters fibroblast growth factor-23 (FGF23) and calcitriol.

The present paper investigated the association of Parkinson’s disease etiology with phosphate toxicity, a pathophysiological condition in which dysregulated phosphate metabolism causes excessive inorganic phosphate sequestration in body tissue that damages organ systems. Excessive phosphate is proposed to reduce Complex I function of the mitochondrial electron transport chain in Parkinson’s disease and is linked to opening of the mitochondrial permeability transition pore, resulting in increased reactive oxygen species, inflammation, DNA damage, mitochondrial membrane depolarization, and ATP depletion causing cell death. Parkinson’s disease is associated with α-synuclein and Lewy body dementia, a secondary tauopathy related to hyperphosphorylation of tau protein, and tauopathy is among several pathophysiological pathways shared between Parkinson’s disease and diabetes. Excessive phosphate is also associated with ectopic calcification, bone mineral disorders, and low levels of serum vitamin D in patients with Parkinson’s disease. Sarcopenia and cancer in Parkinson’s disease patients are also associated with phosphate toxicity. Additionally, Parkinson’s disease benefits are related to low dietary phosphate intake. More studies are needed to investigate the potential mediating role of phosphate toxicity in the etiology of Parkinson’s disease.

Inorganic phosphate (Pi) is essential for maintaining cellular function but excess of Pi leads to serious complications, including vascular calcification. Accumulating evidence suggests that oxidative stress contributes to the pathogenic progression of calcific changes. However, the molecular mechanism underlying Pi-induced reactive oxygen species (ROS) generation and its detrimental consequences remain unclear. Type III Na⁺-dependent Pi cotransporter, PiT-1/-2, play a significant role in Pi uptake of vascular smooth muscle cells. Pi influx via PiT-1/-2 increases the abundance of PiT-1/-2 and depolarization-activated Ca²⁺ entry due to its electrogenic properties, which may lead to Ca²⁺ and Pi overload and oxidative stress. At least four mitochondrial Pi transporters are suggested, among which the phosphate carrier (PiC) is known to be mainly involved in mitochondrial Pi uptake. Pi transport via PiC may induce hyperpolarization and superoxide generation, which may lead to mitochondrial dysfunction and endoplasmic reticulum stress, together with generation of cytosolic ROS. Increase in net influx of Ca²⁺ and Pi and their accumulation in the cytosol and mitochondrial matrix synergistically increases oxidative stress and osteogenic differentiation, which could be prevented by suppressing either Ca²⁺ or Pi overload. Therapeutic strategies targeting plasmalemmal and mitochondrial Pi transports can protect against Pi-induced oxidative stress and vascular calcification.

• Canagliflozin
• Cardiovascular
• Dapagliflozin
• Empagliflozin
• Endothelial
• Hyperphosphatemia
• Phosphate
• Sodium-glucose cotransporter 2

• ESRD
• antioxidants
• calcium carbonate
• oxidative stress markers
• sevelamer hydrochloride

According to the growth rate hypothesis (GRH), tumour cells have high inorganic phosphate (Pi) demands due to accelerated proliferation. Compared to healthy individuals, cancer patients present with a nearly 2.5-fold higher Pi serum concentration. In this work, we show that an increasing concentration of Pi had the opposite effect on Pi-transporters only in MDA-MB-231 when compared to other breast cell lines: MCF-7 or MCF10-A (non-tumoural breast cell line). Here, we show for the first time that high extracellular Pi concentration mediates ROS production in TNBC (MDA-MB-231). After a short-time exposure (1 h), Pi hyperpolarizes the mitochondrial membrane, increases mitochondrial ROS generation, impairs oxygen (O₂) consumption and increases PKC activity. However, after 24 h Pi-exposure, the source of H₂O₂ seems to shift from mitochondria to an NADPH oxidase enzyme (NOX), through activation of PKC by H₂O₂. Exogenous-added H₂O₂ modulated Pi-transporters the same way as extracellular high Pi, which could be reversed by the addition of the antioxidant N-acetylcysteine (NAC). NAC was also able to abolish Pi-induced Epithelial-mesenchymal transition (EMT), migration and adhesion of MDA-MB-231. We believe that Pi transporters support part of the energy required for the metastatic processes stimulated by Pi and trigger Pi-induced H₂O₂ production as a signalling response to promote cell migration and adhesion.

• H+-dependent Pi transport
• Na+-dependent Pi transport
• Pi-induced H2O2 production
• breast cancer cells
• cell migration

• Acetylcysteine/pharmacology
• Breast Neoplasms/drug therapy
• Cell Adhesion
• Cell Line, Tumor
• Cell Movement
• Cell Survival
• Epithelial-Mesenchymal Transition
• Female
• Humans
• Hydrogen Peroxide/chemistry
• MCF-7 Cells
• Membrane Potential, Mitochondrial
• NADPH Oxidases/metabolism
• Neoplasm Metastasis
• Oxygen Consumption
• Phosphates
• Protein Kinase C/metabolism
• Reactive Oxygen Species

Phosphorus (P) is essential for life. As the fifth-most-abundant element in living cells, P is required for the synthesis of an array of biological molecules including (d)NTPs, nucleic acids, and membranes. Organisms typically acquire environmental P as inorganic phosphate (Pi). While essential for growth and viability, excess intracellular Pi is toxic for both bacteria and eukaryotes. Using the bacterium Salmonella enterica serovar Typhimurium as a model, we establish that Pi cytotoxicity is manifested following its assimilation into adenosine triphosphate (ATP), which acts as a chelating agent for Mg²⁺ and other cations. Our findings identify physiological processes disrupted by excessive Pi and how bacteria tune P assimilation to cytoplasmic Mg²⁺ levels.

Phosphorus (P) is an essential component of core biological molecules. In bacteria, P is acquired mainly as inorganic orthophosphate (Pi) and assimilated into adenosine triphosphate (ATP) in the cytoplasm. Although P is essential, excess cytosolic Pi hinders growth. We now report that bacteria limit Pi uptake to avoid disruption of Mg²⁺-dependent processes that result, in part, from Mg²⁺ chelation by ATP. We establish that the MgtC protein inhibits uptake of the ATP precursor Pi when Salmonella enterica serovar Typhimurium experiences cytoplasmic Mg²⁺ starvation. This response prevents ATP accumulation and overproduction of ribosomal RNA that together ultimately hinder bacterial growth and result in loss of viability. Even when cytoplasmic Mg²⁺ is not limiting, excessive Pi uptake increases ATP synthesis, depletes free cytoplasmic Mg²⁺, inhibits protein synthesis, and hinders growth. Our results provide a framework to understand the molecular basis for Pi toxicity. Furthermore, they suggest a regulatory logic that governs P assimilation based on its intimate connection to cytoplasmic Mg²⁺ homeostasis.

• ATP
• MgtC
• Salmonella
• magnesium
• phosphate toxicity

• hyperphosphataemia
• inorganic phosphate
• reactive oxygen species

• Animals
• Cardiovascular Diseases/etiology
• Cardiovascular Diseases/metabolism
• Cardiovascular Diseases/pathology
• Diabetes Mellitus/etiology
• Diabetes Mellitus/metabolism
• Diabetes Mellitus/pathology
• Energy Metabolism
• Humans
• Mitochondria/drug effects
• Mitochondria/pathology
• Muscular Atrophy/etiology
• Muscular Atrophy/metabolism
• Muscular Atrophy/pathology
• Phosphates/pharmacology
• Reactive Oxygen Species/metabolism

• calcium
• fibroblast growth factor 23
• magnesium
• mitochondria
• oxidative stress
• phosphate

• Animals
• Antidotes/pharmacology
• Biological Availability
• Fibroblast Growth Factor-23
• Humans
• Magnesium/pharmacology
• Membrane Potential, Mitochondrial/drug effects
• Oxidative Stress/drug effects
• Phosphates/adverse effects
• Vascular Calcification/etiology

• Chronic kidney disease
• Phosphate
• Phosphorus
• Signaling

• Animals
• Biological Transport
• Extracellular Signal-Regulated MAP Kinases/metabolism
• Humans
• Oncogene Protein v-akt/metabolism
• Phosphates/metabolism
• Receptors, Fibroblast Growth Factor/metabolism
• Signal Transduction
• Sodium-Phosphate Cotransporter Proteins, Type III/metabolism
• raf Kinases/metabolism

• R01 DK107870 NIDDK NIH HHS
• R01 DK125252 NIDDK NIH HHS
• R56 DK107870 NIDDK NIH HHS

• Gene expression
• Inorganic phosphate (P(i))
• Mineralization
• Odontoblasts
• Osteoblasts

• Animals
• Cell Differentiation
• Gene Expression Regulation
• Langer-Giedion Syndrome
• Mice
• Odontoblasts/metabolism
• Phosphates/metabolism
• Repressor Proteins
• Transcription Factors/genetics

• F32 DE029096 NIDCR NIH HHS
• R01 AR074981 NIAMS NIH HHS
• R01 DE023083 NIDCR NIH HHS

The consumption of phosphorus in Western populations largely exceeds the recommended intake, while vitamin D supply is often insufficient. Both situations are linked to an increased cardiovascular risk. A 17-week two-factorial study with Ldl receptor^-/- mice was conducted to investigate the cardiovascular impact of dietary phosphorus [adequate (0.3%; P_0.3) vs. high (1.5%; P_1.5)] in combination with a low (50 IU/kg; D₅₀) or adequate vitamin D diet (1000 IU/kg; D₁₀₀₀). The data demonstrate that mice fed the P_1.5 vs. P_0.3 diets developed smaller vascular lesions (p = 0.013) and cardiac hypotrophy (p = 0.011), which were accompanied by diminished IGF1 and insulin signalling activity in their hearts. Vitamin D showed no independent effect on atherogenesis and heart morphology. Feeding P_1.5 vs. P_0.3 diets resulted in markedly reduced serum triacylglycerols (p < 0.0001) and cholesterol (p < 0.0001), higher faecal lipid excretion (p < 0.0001) and a reduced mRNA abundance of hepatic sterol exporters and lipoprotein receptors. Minor hypocholesterolaemic and hypotriglyceridaemic effects were also found in mice fed the D₁₀₀₀ vs. D₅₀ diets (p = 0.048, p = 0.026). To conclude, a high phosphorus intake strongly affected the formation of vascular lesions, cardiac morphology, and lipid metabolism, although these changes are not indicative of an increased cardiovascular risk.

• Alzheimer’s disease
• Cognitive decline
• Cortisol
• Dementia
• Depression
• Inflammation
• Phosphate toxicity
• Stress

• phosphorus homeostasis
• phosphorus transporter
• transcriptional regulation
• vertebrates

• Animals
• Carps/genetics
• Carps/metabolism
• Cloning, Molecular
• Fish Proteins/genetics
• Fish Proteins/metabolism
• Gene Expression Regulation/drug effects
• Homeostasis/genetics
• Metabolic Networks and Pathways/genetics
• Phosphorus/metabolism
• Phosphorus/pharmacology
• Promoter Regions, Genetic
• Protein Isoforms/genetics
• Protein Isoforms/metabolism
• Response Elements/genetics
• Sequence Analysis, DNA
• Sodium-Phosphate Cotransporter Proteins/genetics
• Sodium-Phosphate Cotransporter Proteins/metabolism
• Sodium-Phosphate Cotransporter Proteins, Type III/genetics
• Sodium-Phosphate Cotransporter Proteins, Type III/metabolism

• 2018YFD0900400 National Key R&D Program of China

Skeletal muscle wasting represents both a common phenotype of aging and a feature of pathological conditions such as chronic kidney disease (CKD). Although both clinical data and genetic experiments in mice suggest that hyperphosphatemia accelerates muscle wasting, the underlying mechanism remains unclear. Here, we showed that inorganic phosphate (Pi) dose-dependently decreases myotube size, fusion index, and myogenin expression in mouse C2C12 skeletal muscle cells. These changes were accompanied by increases in reactive oxygen species (ROS) production and Nrf2 and p62 expression, and reductions in mitochondrial membrane potential (MMP) and Keap1 expression. Inhibition of Pi entry, cytosolic ROS production, or Nrf2 activation reversed the effects of high Pi on Nrf2, p62, and myogenin expression. Overexpression of Nrf2 respectively increased and decreased the promoter activity of p62-Luc and myogenin-Luc reporters. Analysis of nuclear extracts from gastrocnemius muscles from mice fed a high-Pi (2% Pi) diet showed increased Nrf2 phosphorylation in sham-operated and 5/6 nephrectomized (CKD) mice, and both increased p62 phosphorylation and decreased myogenin expression in CKD mice. These data suggest that high Pi suppresses myogenic differentiation in vitro and promotes muscle atrophy in vivo through oxidative stress-mediated protein degradation and both canonical (ROS-mediated) and non-canonical (p62-mediated) activation of Nrf2 signaling.

• Nrf2
• hyperphosphatemia
• muscle wasting
• myogenic differentiation
• oxidative stress

• calcium overload
• hyperphosphatemia
• oxidative stress
• type III sodium-phosphate cotransporters
• vascular calcification
• voltage-gated calcium channel

Doxorubicin (DOXO) chemotherapy increases risk for cardiovascular disease in part by inducing endothelial dysfunction in conduit arteries. However, the mechanisms mediating DOXO-associated endothelial dysfunction in (intact) arteries and treatment strategies are not established.

We tested the hypothesis that DOXO impairs endothelial function in conduit arteries via excessive mitochondrial reactive oxygen species (ROS) and that these effects could be prevented by treatment with a mitochondrial-targeted antioxidant (MitoQ).

Endothelial function (endothelium-dependent dilation [EDD] to acetylcholine) and vascular mitochondrial ROS were assessed 4 weeks following administration (10 mg/kg intraperitoneal injection) of DOXO. A separate cohort of mice received chronic (4 weeks) oral supplementation with MitoQ (drinking water) for 4 weeks following DOXO.

EDD in isolated pressurized carotid arteries was 55% lower 4 weeks following DOXO (peak EDD, DOXO: 42 ± 7% vs. sham: 94 ± 3%; p = 0.006). Vascular mitochondrial ROS was 52% higher and manganese (mitochondrial) superoxide dismutase was 70% lower after DOXO versus sham (p = 0.0008). Endothelial function was rescued by administration of the mitochondrial-targeted antioxidant, MitoQ, to the perfusate. Exposure to plasma from DOXO-treated mice increased mitochondrial ROS in cultured endothelial cells. Analyses of plasma showed differences in oxidative stress-related metabolites and a marked reduction in vascular endothelial growth factor A in DOXO mice, and restoring vascular endothelial growth factor A to sham levels normalized mitochondrial ROS in endothelial cells incubated with plasma from DOXO mice. Oral MitoQ supplementation following DOXO prevented the reduction in EDD (97 ± 1%; p = 0.002 vs. DOXO alone) by ameliorating mitochondrial ROS suppression of EDD.

DOXO-induced endothelial dysfunction in conduit arteries is mediated by excessive mitochondrial ROS and ameliorated by mitochondrial-specific antioxidant treatment. Mitochondrial ROS is a viable therapeutic target for mitigating arterial dysfunction with DOXO.

• chemotherapy
• mitochondrial antioxidant
• reactive oxygen species

• F32 HL151022 NHLBI NIH HHS
• R01 AG055822 NIA NIH HHS
• T32 DK007135 NIDDK NIH HHS

• human sperm
• oxidative stress
• reactive oxygen species
• sperm cryopreservation
• sperm vitrification

• Diabetes
• diabetic nephropathy
• diabetic neuropathy
• diabetic retinopathy
• mitochondria dysfunction
• pancreatic cancer
• phosphate toxicity
• vascular calcification

• Cell Physiological Phenomena
• Cells/metabolism
• Diabetes Complications/etiology
• Diabetes Complications/metabolism
• Diabetes Complications/prevention & control
• Diabetes Mellitus/blood
• Diabetes Mellitus/diet therapy
• Diabetes Mellitus/prevention & control
• Diabetes Mellitus/therapy
• Glucose/metabolism
• Humans
• Micronutrients/adverse effects
• Micronutrients/blood
• Micronutrients/metabolism
• Micronutrients/toxicity
• Phosphates/adverse effects
• Phosphates/blood
• Phosphates/metabolism
• Phosphates/toxicity

The importance of autophagy in parasites with a digenetic life cycle like Leishmania spp. is significant. The parasite survives as promastigotes in the insect gut and as immotile amastigotes in mammals. This study demonstrates increased autophagy in Leishmania parasite during progression of in vitro life cycle and upon exposure to stress stimuli like starvation, oxidative stress, and drugs. Autophagy inhibition during stress exposure increased cell death, indicating the importance of autophagy in cellular defense against adverse conditions. Atg8 protein, a homolog of mammalian autophagy protein LC3 is expressed in Leishmania parasite but its function remains unknown. Overexpression of Atg8 (Atg8-OE) rendered the parasites resistant to stress and capable of infecting macrophages in substantial numbers; however, disruption of the Atg8 gene (ΔAtg8) resulting in suppression of Atg8 protein expression, increased susceptibility to stress and reduced the capability to cause infection. A critical event in the Leishmania parasite lifecycle is the differentiation of promastigote forms to the disease causing amastigote forms. The failure of ΔAtg8 parasites lacking Atg8 protein to differentiate into amastigotes, unlike the Atg8-OE and vector-transfected parasites, clearly indicated Atg8 involvement in a crucial event. The inability of ΔAtg8 parasites to infect macrophages in vitro was verified in an in vivo mouse model of leishmaniases where infection could not be induced by the ΔAtg8 parasites. Autophagy is known to be involved in the remodeling of damaged organelles. The accumulation of Atg8 around damaged mitochondria suggested increase of autophagy in the vicinity of the organelle. This buildup was prevented when mitochondria generated reactive oxygen species that were quenched, suggesting them as possible signaling molecules for sensing mitochondrial instability. In summary, our study provides new evidences for a crucial role of Atg8 protein in sustaining Leishmania parasite survival during life cycle and stress exposure, differentiation to amastigotes, and their infective abilities.

Over 50% of end-stage renal disease (ESRD) patients die of cardiovascular disease. ESRD patients treated with maintenance hemodialysis are repeatedly exposed to oxidative stress. The aim of the study was to find the relationship between lifestyle factors, nutritional status, calcium-phosphate metabolism, and selected redox parameters such as glutathione peroxidase (GPx), glutathione reductase (GR), superoxide dismutase (SOD), uric acid (UA), and total antioxidant capacity expressed as ferric reducing antioxidant power (FRAP). The study included 97 ESRD hemodialysis patients and 42 controls with no renal disease. Patients were asked to complete a questionnaire which gathered information on their physical activity, hours of sleep, smoking, and frequency of fruit and vegetable intake; the blood samples were then drawn before the midweek dialysis session. The ESRD patients had lower levels of GR, GPx, and SOD activity, a lower level of FRAP, and a higher UA concentration than the control group. The FRAP value decreased with age (ρ = −0.32, p = 0.001); smokers had a significantly lower SOD activity in comparison to nonsmokers (p = 0.03). In the ESRD patients, FRAP and UA correlated with both albumin (ρ = 0.26, p = 0.011; ρ = 0.41, p = 0.006, respectively) and prealbumin (ρ = 0.34, p ≤ 0.001; ρ = 0.28, p = 0.006, respectively), whereas UA, GR, GPx, and SOD correlated with calcium, UA, GR, and GPx with phosphate level. Based on the findings, there are weak associations between nutritional status and selected redox parameters in hemodialyzed patients. Further studies are needed to establish if diet modifications and adequate nutritional status can positively impact the antioxidant capacity in this group of patients.

• disulfide
• hypoparathyroidism
• paraoxonase
• thiol
• total antioxidant status
• total oxidant status

• cardiovascular models
• stress signalling

• Cell Line
• Fluoresceins/metabolism
• Humans
• Hydroquinones/pharmacology
• Kelch-Like ECH-Associated Protein 1/biosynthesis
• Kelch-Like ECH-Associated Protein 1/genetics
• Kelch-Like ECH-Associated Protein 1/physiology
• Muscle, Smooth, Vascular/drug effects
• Muscle, Smooth, Vascular/metabolism
• Myocytes, Smooth Muscle/drug effects
• Myocytes, Smooth Muscle/metabolism
• NF-E2-Related Factor 2/physiology
• Oxidation-Reduction
• Oxidative Stress/drug effects
• Phosphates/pharmacology
• Protein Transport/drug effects
• RNA Interference
• RNA, Small Interfering/genetics
• Reactive Oxygen Species/metabolism
• Sequestosome-1 Protein/biosynthesis
• Sequestosome-1 Protein/genetics
• Sequestosome-1 Protein/physiology
• Signal Transduction/physiology
• Up-Regulation
• Vascular Calcification/metabolism
• Vascular Calcification/prevention & control

• Ministry of Education, Science, Sports, and cultrue of Japan

Rapid shifting between extracellular and intracellular phosphorus can occur during dialysis sessions, which can cause aberrant intracellular signaling in long-term hemodialysis (LTHD) patients. However, the effect of these intra-dialysis fluctuations of phosphorus on clinical outcomes has not been examined. Therefore, we investigated the relationship between intradialysis serum phosphorus reduction ratio (IDSPRR) and mortality in LTHD patients.

This was a retrospective, observational cohort study to assess the predictive power of IDSPRR (>0.63 vs. ≤0.63) on mortality in a total of 805 LTHD patients. All these fatal events were analyzed using the Cox proportional hazards regression model.

After multivariable analysis, baseline IDSPRR higher than 0.63 was significantly predictive of all-cause mortality (hazard ratio [HR]: 1.58; 95% confidence interval [CI]: 1.10–2.26), but not for cardiovascular (CV) mortality (HR: 1.41; 95% CI: 0.91–2.18). However, when time-varied IDSPRRs were applied, a value greater than 0.63 was not only significantly predictive of all-cause mortality (HR: 1.74, 95% CI: 1.16–2.63), but also CV mortality (HR: 2.04, 95% CI: 1.23–3.40).

High IDSPRR (>0.63) is independently associated with increased all-cause and CV mortality, which shows the negative effect of rapid intracellular phosphorus-shifting on LTHD patients.

• Cerebrospinal fluid (CSF)
• Fahr's disease
• Idiopathic basal ganglia calcification (IBGC)
• Inorganic phosphorus (Pi)
• Primary familial brain calcification (PFBC)

The recent widespread consumption of Western diets and food additives worldwide is associated with excessive inorganic phosphate intake. However, researchers have known little about the impact of dietary phosphate intake on the development of inflammatory bowel disease to date. In this study, we investigated the effects of dietary phosphate on intestinal inflammation in experimental colitis. Sprague-Dawley rats were fed different phosphate diets (0.5%, 1.0% and 1.5% phosphate) with or without dextran sulfate sodium. For in vitro study, the effects of phosphate on proinflammatory cytokine induction and reactive oxygen species production in RAW264.7 macrophage were examined. Dietary phosphate exacerbated intestinal inflammation in experimental colitis in a dose-dependent manner, as assessed by the clinical disease activity score, colon length, and histology. Furthermore, the high phosphate diet increased myeloperoxidase activity and proinflammatory cytokine mRNA expression through the activation of nuclear factor κB in the inflamed colon. In addition, high phosphate loading in RAW264.7 cells directly enhanced reactive oxygen species production and proinflammatory cytokine gene expression. Our results demonstrated that the high phosphate diet exacerbated intestinal inflammation in experimental colitis. These findings have important therapeutic implications for inflammatory bowel disease patients.

• DSS-induced colitis
• NF-κB
• ROS
• dietary Pi
• proinflammatory cytokine

• endoplasmic reticulum stress
• inorganic phosphate
• mitochondrial permeability transition
• pancreatic β cells
• superoxide

• chronic kidney disease
• fibroblastic growth factor 23
• parathyroid hormone
• phosphate

• Animals
• Bone Diseases/metabolism
• Fibroblast Growth Factor-23
• Fibroblast Growth Factors/metabolism
• Homeostasis/physiology
• Humans
• Hyperparathyroidism, Secondary/metabolism
• Hyperphosphatemia/complications
• Hyperphosphatemia/metabolism
• Hyperphosphatemia/therapy
• Kidney/physiology
• Minerals/metabolism
• Parathyroid Hormone/metabolism
• Phosphates/blood
• Phosphates/physiology
• Phosphorus, Dietary/adverse effects
• Renal Dialysis
• Renal Elimination/physiology
• Renal Insufficiency, Chronic/blood
• Renal Insufficiency, Chronic/metabolism
• Renal Insufficiency, Chronic/therapy
• Vitamin D/metabolism

The present study evaluated the effects of exposing liquid-stored boar semen to different red light LED regimens on sperm quality and reproductive performance. Of all of the tested photo-stimulation procedures, the best pattern consisted of 10 min light, 10 min rest and 10 min of further light (10-10-10 pattern). This pattern induced an intense and transient increase in the majority of motility parameters, without modifying sperm viability and acrosome integrity. While incubating non-photo-stimulated sperm at 37 °C for 90 min decreased all sperm quality parameters, this reduction was prevented when the previously-described light procedure was applied. This effect was concomitant with an increase in the percentage of sperm with high mitochondrial membrane potential. When sperm were subjected to ‘in vitro’ capacitation, photo-stimulation also increased the percentage of sperm with capacitation-like changes in membrane structure. On the other hand, treating commercial semen doses intended for artificial insemination with the 10-10-10 photo-stimulation pattern significantly increased farrowing rates and the number of both total and live-born piglets for parturition. Therefore, our results indicate that a precise photo-stimulation procedure is able to increase the fertilising ability of boar sperm via a mechanism that could be related to mitochondrial function.