Markers Of Cellular Damage Research Articles

HuMSC-EVs Protect Endothelial Cells Against Hypoxia/Reoxygenation Injury by Inhibiting the Pannexin 1/p38-MAPK Pathway

Vascular endothelial cell dysfunction plays an important role in myocardial ischemia–reperfusion (I/R) injury, and pannexin 1 (Panx1), an ATP-permeable channel, is closely associated with the pathophysiological processes of I/R injury. The purpose of this study was to investigate the protective effects of human umbilical cord mesenchymal stromal cell-derived extracellular vesicles (HuMSC-EVs) and the underlying mechanism in a model of I/R injury. For the cellular model of I/R injury, human umbilical vein endothelial cells (HuVECs) were exposed to hypoxia/reoxygenation (H/R) conditions. The model cells were then treated with HuMSC-EVs, and the effects on cell survival and specific signaling activities were observed. The results showed that after H/R exposure, Panx1 expression and other markers of cellular damage were increased in HuVECs. However, treatment with HuMSC-EVs inhibited the H/R-induced increase in Panx1 expression and improved HuVEC survival. Mechanistically, HuMSC-EVs were found to inhibit the p38 mitogen-activated protein kinase (MAPK)-dependent apoptosis pathway, as evidenced by increased Bcl2 expression and reductions in p38 MAPK phosphorylation, Bax expression, and cleaved-caspase 3 expression. Together our data suggest that HuMSC-EVs alleviate H/R-induced apoptosis among HuVECs by inhibiting activity of the Panx1/p38-MAPK-dependent apoptosis pathway.

Soluble biomarkers for Neuromyelitis Optica Spectrum Disorders: a mini review.

The Neuromyelitis Optica Spectrum Disorders (NMOSD) constitute a spectrum of rare autoimmune diseases of the central nervous system characterized by episodes of transverse myelitis, optic neuritis, and other demyelinating attacks. Previously thought to be a subtype of multiple sclerosis, NMOSD is now known to be a distinct disease with unique pathophysiology, clinical course, and treatment options. Although there have been significant recent advances in the diagnosis and treatment of NMOSD, the field still lacks clinically validated biomarkers that can be used to stratify disease severity, monitor disease activity, and inform treatment decisions. Here we review many emerging NMOSD biomarkers including markers of cellular damage, neutrophil-to-lymphocyte ratio, complement, and cytokines, with a focus on how each biomarker can potentially be used for initial diagnosis, relapse surveillance, disability prediction, and treatment monitoring.

Machine Learning Demonstrates Dominance of Physical Characteristics over Particle Composition in Coal Dust Toxicity.

Mine dust has been linked to the development of pneumoconiotic diseases such as silicosis and coal workers' pneumoconiosis. Currently, it is understood that the physicochemical and mineralogical characteristics drive the toxic nature of dust particles; however, it remains unclear which parameter(s) account for the differential toxicity of coal dust. This study aims to address this issue by demonstrating the use of the partial least squares regression (PLSR) machine learning approach to compare the influence of D50 sub 10 μm coal particle characteristics against markers of cellular damage. The resulting analysis of 72 particle characteristics against cytotoxicity and lipid peroxidation reflects the power of PLSR as a tool to elucidate complex particle-cell relationships. By comparing the relative influence of each characteristic within the model, the results reflect that physical characteristics such as shape and particle roughness may have a greater impact on cytotoxicity and lipid peroxidation than composition-based parameters. These results present the first multivariate assessment of a broad-spectrum data set of coal dust characteristics using latent structures to assess the relative influence of particle characteristics on cellular damage.

Abstract 17813: Markers of Cellular Damage, Inflammatory Response, Coagulation and Platelet Activity, and Apoptosis During Catheter Ablation for Atrial Fibrillation Using Radiofrequency and Pulsed-Field Energy

Introduction: Pulsed-field ablation (PFA) presents a new technology for the ablation of AF using non-thermal ablation energy. Ablation energies producing thermal injury are associated with an inflammatory response, platelet activation, and coagulation cascade activation. The study aimed to compare markers of cell damage and platelet and coagulation activation in patients undergoing PVI using PF and radiofrequency (RF) energy. Hypothesis: PFA will be associated will more pronounced myocardial damage, but less pronounced activation of platelets and inflammation. Methods: Patients with AF indicated for PVI were enrolled and randomly assigned to undergo PVI using RF (CARTO Smart Touch, Biosense Webster, USA) or PF (Farapulse, Boston-Scientific, USA) energy. Markers of myocardial damage (high-sensitivity troponin I), apoptosis (Fas ligand, caspase-3), inflammation (interleukin-6), coagulation (D-dimers, Fibrin monomers, von Willebrand antigen and factor activity), platelet activation (P-selectin, activated Gp IIb/IIIa antigen and CD42b), and neuron axon damage (NGF-β) were measured before the procedure (T1), after transseptal puncture, (T2), after completing the ablation in the left atrium (T3), and one day after the procedure (T4). Results: Sixty-five patients were enrolled in the PFA (n=33) and RFA (n=32) groups. Both groups were similar in baseline characteristics (age 60.5±12.7 vs. 64.0±10.7 and 20 (60.6%) non-paroxysmal vs. 20 (62.5%) paroxysmal AF). Procedural and left atrial dwelling times were substantially shorter in the PFA group (55:09±11:57 vs. 151:19±41:25 min, p< 0.001; 36:00±8:05 vs. 115:58±36:49 min, p<0.001). Troponin release (1 d after the procedure) was substantially higher in the PFA group (10,102, IQR 8,272-14,207 vs. 1,006, IQR 603-1,433) and was ten times higher in PFA patients. However, during the procedure, markers of platelet activation, coagulation activation, and inflammation were similar between groups. Conclusions: PF ablation was associated with substantially more myocardial damage compared to radiofrequency ablation. However, coagulation activation, platelet activation, and inflammatory responses were similar.

Increased Presence of Circulating Cell-Free, Fragmented, Host DNA in Pigs Infected with Virulent African Swine Fever Virus.

African swine fever virus (ASFV) causes severe hemorrhagic disease in domestic pigs and wild boar, often with high case fatality rates. The virus replicates in the circulating cells of the monocyte-macrophage lineage and within lymphoid tissues. The infection leads to high fever and a variety of clinical signs. In this study, it was observed that ASFV infection in pigs resulted in a >1000-fold increase in the level of circulating cell-free DNA (cfDNA), derived from the nuclei of host cells in the serum. This change occurred in parallel with the increase in circulating ASFV DNA. In addition, elevated levels (about 30-fold higher) of host mitochondrial DNA (mtDNA) were detected in the serum from ASFV-infected pigs. For comparison, the release of the cellular enzyme, lactate dehydrogenase (LDH), a commonly used marker of cellular damage, was also found to be elevated during ASFV infection, but later and less consistently. The sera from pigs infected with classical swine fever virus (CSFV), which causes a clinically similar disease to ASFV, were also tested but, surprisingly, this infection did not result in the release of cfDNA, mtDNA, or LDH. It was concluded that the level of cfDNA in the serum is a sensitive host marker of virulent ASFV infection.

A new treatment approach: Melatonin and ascorbic acid synergy shields against sepsis-induced heart and kidney damage in male rats

AimTo investigate the combined therapeutic potential of melatonin and ascorbic acid in mitigating sepsis-induced heart and kidney injury in male rats and assess the combination therapy's effects on inflammation, cellular damage, oxidative stress, and vascular function-related markers. Materials and methodsCecal ligation and puncture (CLP) induced sepsis in male rats, which were divided into five groups: Sham, CLP, MEL (melatonin), ASA (ascorbic acid), and MEL+ASA (melatonin and ascorbic acid). Rats were treated, and heart and kidney tissues were collected for biochemical and histopathological analyses. Inflammatory markers (presepsin, procalcitonin, NF-κB, IL-1β, IL-6, TNF-α), cellular damage marker (8-OHDG), oxidative status, nitric oxide (NO), vascular endothelial growth factor (VEGF), and sirtuin 1 (SIRT1) levels were assessed. Key findingsMelatonin and ascorbic acid treatment reduced inflammatory and cellular damage markers compared to the CLP group. Combined treatment improved NO, VEGF levels, and increased SIRT1 expression, suggesting a synergistic effect in mitigating sepsis-induced inflammation, cellular damage, and oxidative stress. Histopathological analyses supported these findings, revealing reduced heart and kidney injury in the MEL+ASA group. SignificanceOur study highlights potential benefits of combining melatonin and ascorbic acid as a therapeutic strategy for alleviating sepsis-induced heart and kidney injury. The synergistic effects of these agents may provide stronger protection against inflammation, oxidative stress, and tissue damage, opening new avenues for future research and clinical applications in sepsis management.

Cardioprotective and renoprotective effects of venlafaxine on cisplatin-induced cardiotoxicity and nephrotoxicity in rats.

The current work aims to demonstrate the potential defensive function of venlafaxine (VLF) in cardiotoxicity and nephrotoxicity caused by cisplatin (CP), that could be by modulating extracellular signal-regulated kinase (ERK)1/2 and nicotinamide adenine dinucleotide phosphate (NAPDH) oxidase NOX4 pathways. Five groups of rats were used, as follow: three control groups (control, carboxymethyl cellulose, and VLF), CP group got CP once (7mg/kg, intraperitoneally, i.p.), and (CP+ VLF) group got CP once then after 1h they got VLF {50mg/kg daily, orally for 14days}. At the end of the study; electrocardiogram (ECG) was recorded for anaesthized rats then blood samples and tissues were taken for biochemical and histopathological investigations. Caspase 3, a marker of cellular damage and apoptosis was detected by immunohistochemistry. CP treatment significantly impaired cardiac functions as evidenced by changes in rats' ECG. Cardiac enzymes, renal markers and inflammatory markers were increased with decreased activities of the total antioxidant capacity, superoxide dismutase and glutathione peroxidase. Also, ERK1/2 and NOX4 were upregulated with histopathological and immunohistochemical alterations of heart and kidney. While, VLF markedly alleviated CP-induced functional cardiac abnormalities and improved ECG pattern. It reduced both cardiac and renal biomarkers, oxidative stress, proinflammatory cytokine with ERK1/2 and NOX4 downregulation, improved the histopathological and immunohistochemical changes induced by cisplatin in heart and kidney. VLF treatment impedes cardiotoxicity and nephrotoxicity caused by CP. This beneficial effect was mediated through reduction of oxidative stress, inflammation, and apoptosis by targeting the ERK1/2 and NOX4.

Respiratory Rate as a Factor in Lung Injury-Not Just What You Set, but How You Set.

Respiratory Rate as a Factor in Lung Injury-Not Just What You Set, but How You Set.

791 CAN ALARMINS BECOME A THERAPEUTIC TARGET FOR A PATIENTS WITH ATRIAL FIBRILLATION?

Abstract The link between alarmins and atrial fibrillation is clear and well known in the literature. We performed a non-systematic review about role of alarmins in pathophysiological mechanism of AF, hypothesizing their role in potential novel therapeutic targets for arrhythmia. Several studies have shown a key role of HMGB1 in AF physiopathology. We have seen an almost direct correlation between HMGB1 and oxidative stress in the inflammatory process of AF. Wu et al. observed that HMGB1 is higher in patients with permanent AF, because they experienced a continuous inflammatory tissue damaging impulse. It was shown a prothrombotic and procoagulative role of HMGB1, increased in patients with AF and atrial thrombosis. Scherschel et al. showed higher concentration of S100β protein in AF patients undergoing catheter ablation. Neuronal injury by intrinsic cardiac autonomic nervous system (ICSN) upon catheter treatment released damage-associated molecular pattern proteins (DAMPs) as S100β protein. In vitro studies dealing with murine intracardiac neuros showed that S100β decreased potential action and increased neuronal cells growth. Many studies demonstrate HSP70 protective role when intracellular, at high concentrations in patients who do not develop arrhythmia after cardiac injury, such as bypass, and low concentrations preoperatively in patients who later develop arrhythmia. At the serum level, on the other hand, it becomes an important marker of cellular damage and oxidative stress, also related to increased IL-2 AND IL-4. Conclusions These results could be considered for new therapeutic strategies, as inhibition of oxidative stress, novel therapeutic targets of anticoagulant drugs and considering alarmins as predictive or prognostic biomarkers of disease.

A unique investigation of thallium, tellurium, osmium, and other heavy metals in recurrent pregnancy loss: A novel approach.

To study the impact of heavy metals especially tellurium, thallium, and osmium, in recurrent pregnancy loss (RPL) and to study their association with antioxidant status and DNA damage. This case-control study included women with RPL (n= 30) and healthy pregnant women as control (n= 30). Following blood collection, serum levels of thallium, tellurium, osmium, lead, mercury, and cadmium were estimated by inductively coupled plasma mass spectrophotometer. Women with RPL exhibited significantly higher levels of heavy metals (P< 0.001) when compared with control women. Intriguingly, increased levels of serum thallium, tellurium, osmium, and lead were negatively correlated with total antioxidant status (P< 0.05). Further, the RPL group demonstrated strong positive correlation between heavy metals (thallium, tellurium, osmium, lead) and DNA damage (P< 0.05). No significant correlation between other heavy metals and markers of cellular damage was noted. Enhanced levels of heavy metals in women with RPL and correlation of thallium, tellurium, osmium, and lead with markers of cellular damage reflect the role of heavy metal poisoning, especially thallium, tellurium, and osmium, as potential risk factor in the etiology underlying recurrent miscarriage.

Neuroprotective Effect of Sovateltide (IRL 1620, PMZ 1620) in a Neonatal Rat Model of Hypoxic-Ischemic Encephalopathy

Therapeutic hypothermia with modest results is the only treatment currently available for neonatal hypoxic ischemic encephalopathy (HIE). Endothelin B (ETB) receptors in the brain are shown to have neural restorative capacity. ETB receptors agonist sovateltide alone or as an adjuvant therapy may enhance neurovascular remodeling in HIE. Sprague-Dawley rat pups were grouped based on treatments into (1) Control; (2) HIE + Vehicle; (3) HIE + Hypothermia; (4) HIE + sovateltide; and (5) HIE + sovateltide + hypothermia. HIE was induced on postnatal day (PND) 7, followed by sovateltide (5 µg/kg) intracerebroventricular injection and/or hypothermia. On PND 10, brains were analyzed for the expression of vascular endothelial growth factor (VEGF), nerve growth factor (NGF), ETB receptors, oxidative stress and cellular damage markers. Vehicle-treated animals had high oxidative stress level as indicated by an increase in lipid peroxidation factor, malondialdehyde, and decreased antioxidants, reduced glutathione and superoxide dismutase, compared to control. These effects were reversed in sovateltide alone (p < 0.001) or in combination with the therapeutic hypothermia (p < 0.001), indicating that ETB receptor activation reduces oxidative stress injury following HIE. Animals receiving sovateltide demonstrated a significant (p < 0.0001) upregulation of ETB receptor, VEGF, and NGF expression in the brain compared to vehicle-treated animals. Additionally, sovateltide alone or in combination with therapeutic hypothermia significantly (p < 0.001) reduced cell death when compared to vehicle or therapeutic hypothermia alone, demonstrating that sovateltide is neuroprotective and attenuates neural damage following HIE. These findings are important and merit additional studies for development of new interventions for improving neurodevelopmental outcomes after HIE.

Increased Levels of Circulating Cell-Free mtDNA in the Plasma of Subjects With Late-Life Depression and Frailty: A Preliminary Study

To evaluate the circulating cell-free mitochondrial DNA (ccf-mtDNA) levels, a marker of cellular stress and damage, in older adults with late-life depression (LLD) and frailty. We hypothesize that individuals with both frailty and LLD will have higher ccf-mtDNA levels than individuals with either condition in isolation. Fifty-three older adults (Never Depressed+Robust (reference group, n=16), LLD+Robust (n=9), Never Depressed+Prefrail/Frail (n=5), and LLD+Prefrail/Frail (n=23)) were included in the study. DNA was extracted from EDTA plasma samples, and ccf-mtDNA was quantified by RT-PCR. We found a statistically significant difference in the levels of ccf-mtDNA across groups (F(3,49)=3.07, p=0.036), with individuals in the LLD+Prefrail/Frail group showing the highest levels of ccf-mtDNA. The coexistence of LLD and frailty is associated with increased markers of cellular damage and stress (i.e., ccf-mtDNA). Our results suggest that these conditions may share cellular stress and mitochondrial dysfunction phenomena as a common biological mechanism, offering potential future opportunities for geroscience-guided interventions for these conditions.

MO472A PRELIMINARY STUDY OF POTENTIAL BIOMARKERS FOR EARLY DIAGNOSIS IN CHRONIC KIDNEY DISEASE

Abstract Background and Aims The conventionally used biomarkers for chronic kidney disease (CKD) diagnosis are not very sensitive for early diagnosis. Their values become clinically significant only when kidney damage is advanced, and a substantial filtration capacity has been lost. The reliance on these biomarkers may result in a long-time lapse in diagnosis, compromising the earlier use of successful therapeutic interventions to prevent CKD progression and reduce the risk of other common comorbidities. The study of earlier and more sensitive biomarkers for CKD diagnosis is an important medical need. Potentially new biomarkers reflecting different pathophysiological processes underlying CKD, such as changes in renal function, tubulointerstitial injury, inflammation and fibrosis, have been proposed. The use of a panel of biomarkers is likely to be synergetic in detecting CKD, since there are several different mechanisms by which CKD can initiate. Our aim was to identify markers of renal damage/dysfunction and evaluate their sensitivity for CKD detection, in patients at the earlier stages of the disease, stages 1 and 2. Method This study included 32 healthy controls and 29 CKD patients at stages 1 and 2, categorized according to the KDIGO guidelines, using the CKD-EPI equation based on serum creatinine to estimate the glomerular filtration rate (GFR). Causes of CKD in the studied patients were diabetes mellitus (n = 19), polycystic kidney disease (n = 1) and of unknown cause (n = 7) or other (n = 2). Circulating levels of creatinine and β-trace protein (BTP), as markers of renal function; interleukin 6 (IL-6), as a marker of inflammation; tissue inhibitor metalloproteinase 1 (TIMP 1), as a marker of tubulointerstitial injury; pro B-type natriuretic peptide (proBNP), as a marker of cardio-renal dysfunction; and cell-free DNA (cfDNA), as a marker of cellular damage, were evaluated. Results Compared to controls, we found significantly higher values of all studied markers in CKD patients (stage 1 and stage 2): BTP, TIMP-1, IL-6, pro-BNP, and cfDNA. In CKD patients, GFR was negatively correlated with circulating levels of pro-BNP (r = -0.610, P = 0.004, n = 20) and cfDNA (r = -0.408, P = 0.028, n = 29); and, microalbuminuria was positively correlated with circulating levels of BTP (r = 0.465, P = 0.013, n = 28). The biomarker cfDNA was positively correlated with TIMP-1 (r = 0.445, P = 0.16, n = 29) , a marker of tubulointerstitial injury, and with IL-6 (r = 0.670, P &amp;lt; 0.001, n = 29), a marker of inflammation. All patients presented at least two of the studied biomarkers with higher values than the median value presented by controls. Of all studied biomarkers, BTP was the one that was most altered in patients (86.2% presented higher values than the highest value presented by controls). Conclusion Our results suggest that the studied biomarkers are sensitive to the primary response to renal injury, being significantly elevated in the earlier stages of CKD, particularly BTP. Pro-BNP and cfDNA correlate well with disease severity assessed by GFR. The use of a panel comprising several biomarkers, related with different pathophysiological mechanisms underlying CKD initiation and progression, may increase the potential to detect patients at risk, when compared with the evaluation of each biomarker alone. Further validation for the use of these new potential biomarkers requires larger studies with standardized analytical methodologies. Acknowledgments: This work was supported by Applied Molecular Biosciences Unit (UCIBIO) and financed by FEDER COMPETE2020 funds UIDB/04378/2020 and UIDP/04539/2020 (CIBB); by POCI-01-0145-FEDER-007440; by FCT doctoral grant SFRH/BD/145939/2019; by funds from Portugal Regional Coordination and Development Commissions (Norte-01-0145-FEDER-000024).

Tideglusib inhibition of GSK3 promotes the oxidative muscle phenotype and reduces serum creatine kinase in D2 mdx mice

Introduction Duchenne muscular dystrophy (DMD) is an X-linked disorder caused by an absence of dystrophin that compromises membrane integrity, ultimately resulting in muscle weakness, wasting, and premature death. The fast glycolytic muscle fibres are known to be most susceptible to dystrophic pathology, while slow oxidative fibres are less affected. Thus, promoting the slow oxidative phenotype has become a viable therapeutic strategy. Recent work from our lab has shown that inhibiting the enzyme glycogen synthase kinase 3 (GSK3) can promote the slow oxidative phenotype leading to enhancements in fatigue resistance. Furthermore, we have shown that inhibiting GSK3 augments muscle specific force production and myoblast fusion. Therefore, inhibiting GSK3 may aid in alleviating dystrophic pathology. Tideglusib is a potent GSK3 inhibitor currently undergoing clinical trials for myotonic dystrophy, another form of muscular dystrophy. Here, we tested whether treating the DMD preclinical mdx mouse with tideglusib would alter muscle oxidative phenotype, improve muscle function, and reduce serum creatine kinase (CK) levels, a marker of cellular damage. Methods Male DBA/2J wild type (WT) and mdx mice were ordered from Jackson Laboratories at 5-6 weeks of age. Three groups were included in this study; 1) WT healthy control, 2) mdx tideglusib (10 mg/kg/day, via oral gavage), and 3) mdx vehicle (26% peg400, 15% Chremaphor EL and water). The mdx-tideglusib and vehicle mice underwent their respective treatments for 2 weeks with ad libitum access to food and water. Subsequently, all mice were subjected to a hangwire test to assess muscle function. Mice were then euthanized and their serum extracted for CK activity analyses using a commercially available kit that was fitted onto a 96-well plate. Extensor digitorum longus (EDL) muscles were collected and homogenized for Western blotting to investigate phosphorylated (serine 9) and total GSK3b content along with myosin heavy chain (MHC) I and IIa levels. Results The hangwire test results showed that mdx mice treated with tideglusib were able to sustain hanging on the wire for a significantly longer period of time compared with the mdx vehicle group (p = 0.03). Serum CK analyses revealed that while the mdx vehicle group had significantly higher levels of activity compared with WT (p = 0.009), there was a 30% reduction in the mdx tideglusib mice that was no longer significantly different from WT. Western blotting revealed that though phosphorylated GSK3b levels were unaltered, tideglusib treatment led to a significant reduction in GSK3b content compared with vehicle (p = 0.04). Additionally, there was a significant increase in the oxidative MHC isoforms (I and IIa, p = 0.02) in the mdx tideglusib group compared with vehicle. Conclusions Our results demonstrate the potential use of tideglusib for DMD. We show that tideglusib treatment inhibited GSK3 in mdx mice through a reduction in total GSK3 content. In turn, we also found a significant increase in oxidative MHC isoforms (I and IIa), which was associated with enhanced muscle performance and reduced muscle damage.

Effects of dietary florfenicol contained feeds on growth and immunity of European seabass (Dicentrarchus labrax) in flow-through and recirculating aquaculture system

Antibiotic growth promoters have been banned in animal husbandry and aquaculture in China, since 2020. Florfenicol (FLO) is the most used antibiotics in aquaculture for controlling various bacterial disease in fish, although its effect on health of farmed fish remains a concern. In the present study, European seabass (Dicentrarchus labrax) reared under flow-through aquaculture system (FAS) and recirculating aquaculture system (RAS), were fed on diets supplemented with FLO for 10 d, followed by a 20-d withdrawal period. The effects of FLO on the growth performance, intestinal digestive enzyme activities, serum biochemical parameters, antioxidant enzymes, and expression of related genes, were evaluated. The results showed that FLO exposure inhibited growth performance of D. labrax although this was recovered after stopping the feeding. Besides, FLO suppressed α-Amylase and trypsin activities in the intestine, and the amounts of nutrition-related indicators were also affected. In addition, FLO exposure upregulated liver cellular damage markers (ALT, ALP, and AST) during the treatment phase, although it did not pose a high potential for liver damage. We also observed elevated levels of SOD, CAT, and MDA in gills, indicative of oxidative stress on the cultured fish. Moreover, integrated biomarker response results indicated that fish in RAS had higher growth performance and immunity in the late post-treatment phase, relative to those in RAS, after FLO exposure. This was attributed to high-efficient water treatment of RAS. Overall, these results indicate that exposure to FLO modulates digestive enzyme activities and antioxidant response in European seabass, thereby affecting their growth performance and immune response under different aquaculture modes.

Artificial light at night interacts with predatory threat to alter reef fish metabolite profiles

Light cycles and predatory threat define activity patterns (e.g. feeding/sleeping, activity/rest) in most diurnal fish species. Artificial light at night (ALAN) may disrupt natural cycles and biochemical processes, a mismatch which can eventually reduce condition and fitness. We evaluate the separate and joint effects of ALAN and predator threat on metabolism within brain, liver and muscle tissue of a common, wild caught damselfish, blue green chromis (Chromis viridis). The effects of ALAN varied according to tissue type and predator exposure. In all tissues we observed changes in metabolic pathways associated with increased activity under continuous light (despite provision of shelter), specifically those associated with energy metabolism, cell signalling, responses to oxidative stress and markers of cellular damage. In both the brain and liver tissues, predator threat served to moderate the influence of ALAN on metabolic change, likely due to increased sheltering behaviour. However, no interaction of predator threat with ALAN was observed in metabolism of the muscle tissue. Our results highlight complex sub-acute effects of ALAN exposure on tissue specific and whole organism energy metabolism. Collectively these effects indicate that ALAN has significant scope to reduce fitness of coastal fishes and potentially threaten ecosystem services, but that these changes are highly complex and may be altered by biotic drivers of activity.

Use of Creatine and Creatinine to Minimize Doxorubicin-Induced Cytotoxicity in Cardiac and Skeletal Muscle Myoblasts

Doxorubicin (DOX), an effective anticancer agent, can damage cardiac and skeletal muscle tissue via excessive generation of reactive oxygen species (ROS). Supplemental creatine (Cr) has been shown to have a therapeutic role in disease states characterized by increased oxidative stress. To investigate the effects of Cr and creatinine (CrN) on DOX-induced cytotoxicity. Cultured L6 and H9C2 myoblasts were exposed to 25 μM DOX, 10 mM Cr, 10 mM CrN, 25 μM DOX + 10 mM Cr, 25 μM DOX + 10 mM CrN, or control media for 12 h. Viability was assessed using Confocal and Widefield imaging. Immunoblotting was used to determine protein expression. Viability was lowest in the DOX-treated group regardless of cell type; however, when DOX was combined with Cr or CrN, viability was improved. Levels of oxidative stress, as measured by 4-hydroxynonenal (4HNE), were significantly (p < 0.05) higher in the DOX treated cells vs. controls; however, Cr + DOX and CrN + DOX significantly lowered 4HNE levels compared to DOX-treated cells. Creatine kinase (CK), a key marker of cellular damage, was significantly higher in DOX-treated H9c2 cells vs. controls. However, Cr or CrN in combination with DOX, resulted in no significant differences in CK vs. controls. Supplementation with Cr or CrN may preserve cell viability during DOX treatment.

Microwaves from mobile phone induce reactive oxygen species but not DNA damage, preleukemic fusion genes and apoptosis in hematopoietic stem/progenitor cells

Exposure to electromagnetic fields (EMF) has been associated with the increased risk of childhood leukemia, which arises from mutations induced within hematopoietic stem cells often through preleukemic fusion genes (PFG). In this study we investigated whether exposure to microwaves (MW) emitted by mobile phones could induce various biochemical markers of cellular damage including reactive oxygen species (ROS), DNA single and double strand breaks, PFG, and apoptosis in umbilical cord blood (UCB) cells including CD34+ hematopoietic stem/progenitor cells. UCB cells were exposed to MW pulsed signals from GSM900/UMTS test-mobile phone and ROS, apoptosis, DNA damage, and PFG were analyzed using flow cytometry, automated fluorescent microscopy, imaging flow cytometry, comet assay, and RT-qPCR. In general, no persisting difference in DNA damage, PFG and apoptosis between exposed and sham-exposed samples was detected. However, we found increased ROS level after 1 h of UMTS exposure that was not evident 3 h post-exposure. We also found that the level of ROS rise with the higher degree of cellular differentiation. Our data show that UCB cells exposed to pulsed MW developed transient increase in ROS that did not result in sustained DNA damage and apoptosis.

The Source and Pathophysiologic Significance of Excreted Cadmium.

In theory, the identification of the source of excreted cadmium (Cd) might elucidate the pathogenesis of Cd-induced chronic kidney disease (CKD). With that possibility in mind, we studied Thai subjects with low, moderate, and high Cd exposure. We measured urine concentrations of Cd, ([Cd]u); N-acetyl-β-d-glucosaminidase, a marker of cellular damage ([NAG]u); and β2-microglobulin, an indicator of reabsorptive dysfunction ([β2MG]u). To relate excretion rates of these substances to existing nephron mass, we normalized the rates to creatinine clearance, an approximation of the glomerular filtration rate (GFR) (ECd/Ccr, ENAG/Ccr, and Eβ2MG/Ccr). To link the loss of intact nephrons to Cd-induced tubular injury, we examined linear and quadratic regressions of estimated GFR (eGFR) on ECd/Ccr, eGFR on ENAG/Ccr, and ENAG/Ccr on ECd/Ccr. Estimated GFR varied inversely with both ratios, and ENAG/Ccr varied directly with ECd/Ccr. Linear and quadratic regressions of Eβ2MG/Ccr on ECd/Ccr and ENAG/Ccr were significant in moderate and high Cd-exposure groups. The association of ENAG/Ccr with ECd/Ccr implies that both ratios depicted cellular damage per surviving nephron. Consequently, we infer that excreted Cd emanated from injured tubular cells, and we attribute the reduction of eGFR to the injury. We suggest that ECd/Ccr, ENAG/Ccr, and eGFR were associated with one another because each parameter was determined by the tubular burden of Cd.

Individualized exercise and the health of the AYA cancer survivor population

Background + Hypothesis&#x0D; Adolescent and young adult cancer survivors (AYACS: ages 15-39) have an 84.5% five-year survival rate.(1) AYACS have a 10 times greater risk to develop cardiac disease compared to healthy peers.(2) This is in part due to their lower physical activity.(3) Structured exercise in adult cancer survivors improves strength, fatigue, VO2, and antioxidant levels and it decreases markers of cellular damage(4, 5). AYACS could benefit similarly, reducing long-term health effects. Although evidence suggests exercise is beneficial in older cancer survivors, this has not been demonstrated in AYACS. We hypothesized that a 12-week one-on-one multi-modal, community-based exercise program would improve AYACS outcomes compared to baseline or inactive AYACS. The current study hopes to demonstrate the feasability of an exercise intervention in a community setting within Indianapolis.&#x0D; Methods&#x0D; Six individuals were included in a feasibility trial for a larger pilot study of 374 participants. On day 1, baseline assessments were performed for experimental outcomes: body composition, strength, flexibility, VO2peak, balance, plasma biomarkers, PA, psychological health, health-related quality of life, and fatigue. Mini reassessments were performed at week 5, measuring strength and VO2peak with an estimated 1-rep maximum and 6-minute Walk Test respectively; in the larger pilot study participants will be reassessed at weeks 12 and 24. Participants train for 60 minutes (20 cardio, 30 weights, 10 stretching) 3 times a week for 12 weeks, one-on-one with a cancer exercise specialist.&#x0D; Results&#x0D; The average change in VO2peak was +25.3% and in strength was +17.5% (no statistical analysis). Adherence was 90.9%.&#x0D; Conclusion + Potential impact&#x0D; This trial suggests the feasibility of a pilot larger study. The greatest limitation was that the population sample was not within the AYACS age range. However, as the goal was to show feasibility rather than to prove efficacy, the sample gave useful information.&#x0D; Sources (1-5) 1. Anderson C, Smitherman AB, Nichols HB. Conditional relative survival among long-term survivors of adolescent and young adult cancers. Cancer. 2018;124(14):3037-43. 2. Armstrong GT, Kawashima T, Leisenring W, Stratton K, Stovall M, Hudson MM, et al. Aging and risk of severe, disabling, life-threatening, and fatal events in the childhood cancer survivor study. J Clin Oncol. 2014;32(12):1218-27. 3. Wu YP, Yi J, McClellan J, Kim J, Tian T, Grahmann B, et al. Barriers and Facilitators of Healthy Diet and Exercise Among Adolescent and Young Adult Cancer Survivors: Implications for Behavioral Interventions. J Adolesc Young Adult Oncol. 2015;4(4):184-91. 4. Repka CP, Hayward R. Oxidative Stress and Fitness Changes in Cancer Patients after Exercise Training. Med Sci Sports Exerc. 2016;48(4):607-14. 5. Repka CP, Hayward R. Effects of an Exercise Intervention on Cancer-Related Fatigue and Its Relationship to Markers of Oxidative Stress. Integr Cancer Ther. 2018;17(2):503-10.