Organ-specific Biomarkers Research Articles

Targeting Sepsis: Disease Tolerance, Immune Resilience, and Compartmentalized Immunity

Introduction: Sepsis remains a major contributor to critical care mortality and morbidity worldwide. Despite advances in understanding its complex immunopathology, the compartmentalized nature of immune responses across different organs has yet to be fully translated into targeted therapies. This review explores the burden of sepsis on organ-specific immune dysregulation, immune resilience, and epigenetic reprogramming, emphasizing translational challenges and opportunities. Methods: We implemented a systematic literature search strategy, incorporating data from studies published between 2010 and 2024, to evaluate the role of molecular profiling techniques, including transcriptomics and epigenetic markers, in assessing the feasibility of targeted therapies. Results: Sepsis-induced immune dysregulation manifests differently in various organs, with lung, heart, liver, and kidney responses driven by unique local immune environments. Organ-specific biomarkers, such as the Spns2/S1P axis in lung macrophages, mitochondrial dysfunction in the heart, proenkephalin for early acute kidney injury (AKI), and adrenomedullin for predicting multi-organ failure, offer promising avenues for timely intervention. Furthermore, immune resilience, particularly through regulatory T-cell modulation and cytokine targeting (e.g., IL-18), is crucial for long-term recovery. Epigenetic mechanisms, including histone modification and trained immunity, present opportunities for reprogramming immune responses but require more precision to avoid unintended inflammatory sequelae. Conclusions: A deeper understanding of compartmentalized immune responses and the dynamic immune landscape in sepsis is critical for developing precision therapies. Real-time immune monitoring and organ-targeted interventions could revolutionize sepsis management, although significant barriers remain in clinical translation. Further research is required to establish biomarkers and treatment timing that optimize therapeutic efficacy while minimizing systemic risks.

Deciphering Ferroptosis: From Molecular Pathways to Machine Learning-Guided Therapeutic Innovation.

Ferroptosis is a unique form of cell death reliant on iron and lipid peroxidation. It disrupts redox balance, causing cell death by damaging the plasma membrane, with inducers acting through enzymatic pathways or transport systems. In cancer treatment, suppressing ferroptosis or circumventing it holds significant promise. Beyond cancer, ferroptosis affects aging, organs, metabolism, and nervous system. Understanding ferroptosis mechanisms holds promise for uncovering novel therapeutic strategies across a spectrum of diseases. However, detection and regulation of this regulated cell death are still mired with challenges. The dearth of cell, tissue, or organ-specific biomarkers muted the pharmacological use of ferroptosis. This review covers recent studies on ferroptosis, detailing its properties, key genes, metabolic pathways, and regulatory networks, emphasizing the interaction between cellular signaling and ferroptotic cell death. It also summarizes recent findings on ferroptosis inducers, inhibitors, and regulators, highlighting their potential therapeutic applications across diseases. The review addresses challenges in utilizing ferroptosis therapeutically and explores the use of machine learning to uncover complex patterns in ferroptosis-related data, aiding in the discovery of biomarkers, predictive models, and therapeutic targets. Finally, it discusses emerging research areas and the importance of continued investigation to harness the full therapeutic potential of targeting ferroptosis.

Combination of ST2 With Organ-Specific Biomarker is More Sensitive and Specific for the Diagnosis of Acute Graft-vs-Host Disease

Diagnosis of acute graft-vs-host disease (aGVHD) based on clinical symptoms and biopsy of involved organ was not satisfactory; reliable plasma biomarkers or their panels would be of great value to increase the sensitivity and specificity for such a fatal complication. One hundred two patients who received allogeneic hematopoietic stem cell transplantation in our center were included in this study. Systemic biomarkers of ST2, IP10, IL-2Rα, TNFR1, and organ-specific biomarkers of Elafin, REG-3α, and KRT-18F in plasma were tested by ELISA. The correlation of each biomarker or selected panel of some systemic and organ-specific biomarker with aGVHD was investigated. The level of each systemic biomarker in aGVHD patients was significantly higher than that in patients without aGVHD. Organ-specific biomarker of Elafin, REG-3α, and KRT-18F also had predictive value for aGVHD of skin, gastrointestinal tract, and liver, respectively. Combination of ST2 with one of the 3 organ-specific biomarkers could provide more accurate prediction for aGVHD with skin, gastrointestinal tract, and liver, respectively. All the biomarkers tested in our study correlated with the severity and clinical course of aGVHD. Combination of each systemic biomarker with organ-specific biomarker could increase the sensitivity and specificity for the diagnosis of aGVHD, whereas ST2 with organ-specific biomarker is more sensitive for the diagnosis of organ-specific aGVHD.

Biomarkers of heatstroke-induced organ injury and repair.

What is the topic of this review? The status and potential role of novel biological markers (biomarkers) that can help identify the patients at risk of organ injury or long-term complications following heatstroke. What advances does it highlight? Numerous biomarkers were identified related to many aspects of generalized heatstroke-induced cellular injury and tissue damage, and heatstroke-provoked cardiovascular, renal, cerebral, intestinal and skeletal muscle injury. No novel biomarkers were identified for liver or lung injury. Classic and exertional heatstroke cause acute injury and damage across numerous organ systems. Moreover, heatstroke survivors may sustain long-term neurological, cardiovascular and renal complications with a persistent risk of death. In this context, biomarkers, defined as biological samples obtained from heatstroke patients, are needed to detect early organ injury, and predict outcomes to develop novel organ preservation therapeutic strategies. This narrative review provides preliminary insights that will guide the development and future utilization of these biomarkers. To this end, we have identified numerous biomarkers of widespread heatstroke-associated cellular injury, tissue damage and repair (extracellular heat shock proteins 72 and 60, high mobility group box protein 1, histone H3, and interleukin-1α), and other organ-specific biomarkers including those related to the cardiovascular system (cardiac troponin I, endothelium-derived factors, circulation endothelial cells, adhesion molecules, thrombomodulin and von Willebrand factor antigen), the kidneys (plasma and urinary neutrophil gelatinase-associated lipocalin), the intestines (intestinal fatty acid-binding protein 2), the brain (serum S100β and neuron-specific enolase) and skeletal muscle (creatine kinase, myoglobin). No specific biomarkers have been identified so far for liver or lung injury in heatstroke. Before translating the identified biomarkers into clinical practice, additional preclinical and clinical prospective studies are required to further understand their clinical utility, particularly for the biomarkers related to long-term post-heatstroke health outcomes.

Multi-Organ Dysfunction in Cerebral Palsy.

Cerebral Palsy (CP) describes a heterogenous group of non-progressive disorders of posture or movement, causing activity limitation, due to a lesion in the developing brain. CP is an umbrella term for a heterogenous condition and is, therefore, descriptive rather than a diagnosis. Each case requires detailed consideration of etiology. Our understanding of the underlying cause of CP has developed significantly, with areas such as inflammation, epigenetics and genetic susceptibility to subsequent insults providing new insights. Alongside this, there has been increasing recognition of the multi-organ dysfunction (MOD) associated with CP, in particular in children with higher levels of motor impairment. Therefore, CP should not be seen as an unchanging disorder caused by a solitary insult but rather, as a condition which evolves over time. Assessment of multi-organ function may help to prevent complications in later childhood or adulthood. It may also contribute to an improved understanding of the etiology and thus may have an implication in prevention, interventional methods and therapies. MOD in CP has not yet been quantified and a scoring system may prove useful in allowing advanced clinical planning and follow-up of children with CP. Additionally, several biomarkers hold promise in assisting with long-term monitoring. Clinicians should be aware of the multi-system complications that are associated with CP and which may present significant diagnostic challenges given that many children with CP communicate non-verbally. A step-wise, logical, multi-system approach is required to ensure that the best care is provided to these children. This review summarizes multi-organ dysfunction in children with CP whilst highlighting emerging research and gaps in our knowledge. We identify some potential organ-specific biomarkers which may prove useful in developing guidelines for follow-up and management of these children throughout their lifespan.

Attenuation of arsenic induced high fat diet exacerbated oxidative stress mediated hepatic and cardiac injuries in male Wistar rats by piperine involved antioxidative mechanisms

The current study explored the efficacy of piperine in attenuating arsenic induced high fat diet aggravated oxidative stress mediated injury in hepatic and cardiac tissues of male Wistar rats. Oral administration of piperine significantly (p < 0.05) reduced the levels of organ specific and oxidative stress biomarkers in arsenic and high fat diet treated rat hepatic and cardiac tissues in a dose dependant manner with the dose of 60 mg/kg b.w. exhibiting maximum protection. Arsenic induced high fat diet aggravated oxidative stress mediated damages in liver and heart tissues led to decreased activities of antioxidant enzymes, ROS generation, diminished activities of Krebs’ cycle and respiratory chain enzymes, collapsed mitochondrial membrane potential, mitochondrial DNA damage along with altered lipid metabolism and inflammatory cytokine levels. Histochemical and histopathological studies supported the above findings. Piperine efficiently counteracted the arsenic induced high fat diet aggravated oxidative stress mediated damages by modulating antioxidant defense mechanism along with free radical quenching ability. These findings indicate that piperine protected the arsenic induced high fat diet aggravated hepatic and cardiac injuries which underline the importance of piperine in providing a possible therapeutic regime for the amelioration of arsenic-induced high fat diet aggravated oxidative stress mediated organ damages.

Stimulation of Alpha1-Adrenergic Receptor Ameliorates Cellular Functions of Multiorgans beyond Vasomotion through PPARδ.

Cells can shift their metabolism between glycolysis and oxidative phosphorylation to enact their cell fate program in response to external signals. Widely distributed α1-adrenergic receptors (ARs) are physiologically stimulated during exercise, were reported to associate with the activating energetic AMPK pathway, and are expected to have biological effects beyond their hemodynamic effects. To investigate the effects and mechanism of AR stimulation on the physiology of the whole body, various in vitro and in vivo experiments were conducted using the AR agonist midodrine, 2-amino-N-[2-(2,5-dimethoxyphenyl)-2-hydroxy-ethyl]-acetamide. The expression of various biomarkers involved in ATP production was estimated through Western blotting, reverse transcription polymerase chain reaction, oxygen consumption rate, enzyme-linked immunosorbent assay (ELISA), fluorescence staining, and Oil red O staining in several cell lines (skeletal muscle, cardiac muscle, liver, macrophage, vascular endothelial, and adipose cells). In spontaneously hypertensive rats, blood pressure, blood analysis, organ-specific biomarkers, and general biomolecules related to ATP production were measured with Western blot analysis, immunohistochemistry, ELISA, and echocardiography. Pharmacological activation of α1-adrenergic receptors in C2C12 skeletal muscle cells promoted mitochondrial oxidative phosphorylation and ATP production by increasing the expression of catabolic molecules, including PPARδ, AMPK, and PGC-1α, through cytosolic calcium signaling and increased GLUT4 expression, as seen in exercise. It also activated those energetic molecules and mitochondrial oxidative phosphorylation with cardiomyocytes, endothelial cells, adipocytes, macrophages, and hepatic cells and affected their relevant cell-specific biological functions. All of those effects occurred around 3 h (and peaked 6 h) after midodrine treatment. In spontaneously hypertensive rats, α1-adrenergic receptor stimulation affected mitochondrial oxidative phosphorylation and ATP production by activating PPARδ, AMPK, and PGC-1α and the relevant biologic functions of multiple organs, suggesting organ crosstalk. The treatment lowered blood pressure, fat and body weight, cholesterol levels, and inflammatory activity; increased ATP content and insulin sensitivity in skeletal muscles; and increased cardiac contractile function without exercise training. These results suggest that the activation of α1-adrenergic receptor stimulates energetic reprogramming via PPARδ that increases mitochondrial oxidative phosphorylation and has healthy and organ-specific biological effects in multiple organs, including skeletal muscle, beyond its vasomotion effect. In addition, the action mechanism of α1-adrenergic receptor may be mainly exerted via PPARδ.

Abstract 199: TNF-Alpha Response After Experimental Cardiac Arrest in Rats is Not Attenuated by Thalidomide

Background: Resuscitation from cardiac arrest (CA) results in systemic cytokines response, and neuroinflammation. Thalidomide has been reported to selectively decrease tumor necrosis factor alpha (TNFa) and shown to be neuroprotective. Hypothesis: Thalidomide would decrease systemic and organ-specific cytokine response and biomarkers of injury after CA in rats. Methods: Adult male rats were subjected to 10 min ventricular fibrillation CA. Three groups were studied (n=4-6 per group): naives, CA treated with vehicle and CA treated with thalidomide (CA+T, 50 mg/kg i.p.). TNFa was assessed at 3 h in the cortex, hippocampus, striatum, cerebellum, plasma, heart and lung (Luminex). NSE and S100b were used to assess neuronal and glial injury, cardiac troponin I (cTnI) cardiac ichemia and IFABP to assess intestinal damage (ELISA). Results: CA resulted in a robust increase of TNFa in plasma (Figure 1) and tissues (Figure 2) with no differences between CA and CA+T groups in any region. NSE, S100b, cTnI and IFABP were increased after CA or CA+T vs. naives (all p&lt;0.05) without differences between CA vs. CA+T. Conclusions: CA resulted in an early massive TNFa response systemically and in target organs, with increased biomarkers of organ injury. Thalidomide in a dose reported previously to improve outcome of in vivo models of brain ischemia did not decrease TNFa levels in plasma, brain or extracerebral organs, or biomarkers of injury in our model of experimental CA. Cytokine response to CA was identified as a therapeutic target for future interventions on systemic and end-organ levels. Other promising anti-TNFa strategies incl. anti-TNFa antibodies are currently being evaluated in CA models.

Cell-Based Vital Organs Specific Biomarkers Assessment using Biofield Energy Based Novel Test Formulation

The aim of the present study was to determine the impact of Biofield Energy Treated test formulation using six differentcell-lines. The test formulation/item (TI) and cell media (Med) was divided into two parts; one part was untreated (UT) and other part received Biofield Energy Treatment remotely by a renowned Biofield Energy Healer, Janice Patricia Kinney, USA and labeled as Biofield Energy Treated (BT) test item (TI)/media. Based on cell viability assay, test formulation was found as safe at tested concentrations. Cytoprotective activity of test formulation showed a significant restoration of cell viability by 60.6% (10 µg/mL), 67.5% (63.75 µg/mL), and 117.5% (63.75 µg/mL) in UT-Med + BT-TI, BT-Med + UT-TI, BT-Med + BT-TI, respectively compared to untreated in human cardiac fibroblasts cells (HCF) cells. Moreover, restoration of cell viability was improved by 64% and 127.3% in UT-Med + BT-TI and BT-Med + UT-TI, respectively at 1 µg/mL compared to untreated in human liver cancer (HepG2) cells. Cellular restoration in A549 cells was improved by 314% and 112.3% at 1 µg/mL in BT-Med + UT-TI and BT-Med + BT-TI, respectively than untreated. ALP activity in Ishikawa cells was significantly increased by 175.5%, 547.2%, and 220.8% in UT-Med + BT-TI, BT-Med + UT-TI, and BT-Med + BT-TI, respectively at 0.1 µg/mL as compared to untreated. Additionally, in MG-63 cells showed increased ALP activity by 76.9%, 78.4%, and 79% in UT-Med + BT-TI, BT-Med + UT-TI, and BT-Med + BT-TI, respectively at 50 µg/mL compared to untreated. The percent cellular protection of HCF (heart) cells (decreased of LDH activity) was significantly increased by 60.6% (10 µg/mL), 67.5% (63.75 µg/mL), and 117.5% (63.75 µg/mL) in UT-Med + BT-TI, BT-Med + UT-TI, and BT-Med + BT-TI, respectively as compared to untreated. An improved HepG2 cells protection (represents decreased ALT activity) by 115.1% (1 µg/mL), 42.5% (25.5 µg/mL), and 60.8% (10 µg/mL) in UT-Med + BT-TI, BT-Med + UT-TI, BT-Med + BT-TI, respectively as compared to untreated. Percentage cellular protection of A549 (lungs) cells (represents increased of SOD activity) was significantly increased by 191.1% and 81.4% at 0.1 µg/mL in UT-Med + BT-TI and BT-Med + BT-TI, respectively as compared to untreated. Serotonin level was significantly increased by 31.8% (10 µg/mL) and 56.9% (25.5 µg/mL) in UT-Med + BT-TI and BT-Med + BT-TI, respectively compared to untreated in human neuroblastoma cells (SH-SY5Y). Relative quantification (RQ) of vitamin D receptor (VDR) was significantly increased by 304.3% (0.01 µg/mL), 128.4% (0.1 µg/mL), and 240% (0.1 µg/mL) in UT-Med + BT-TI, BT-Med + UT-TI, and BT-Med + BT-TI, respectively compared to untreated in MG-63 cells. Thus, Biofield Energy Treated test formulation (The Trivedi Effect®) significantly improved organ specific functional biomarkers and would be useful for multiple organs health related to coronary artery disease, arrhythmias, congenital heart disease, cardiomyopathy, cirrhosis, liver cancer, hemochromatosis, asthma, chronic bronchitis, cystic fibrosis, osteoporosis, etc.

Role of the Biofield Energy Treated Test Formulation on Different Vital Organ Specific Biomarkers

Role of the Biofield Energy Treated Test Formulation on Different Vital Organ Specific Biomarkers

Assessment of Drug-Induced Toxicity Biomarkers in the Brain Microphysiological System (MPS) Using Targeted and Untargeted Molecular Profiling.

Early assessment of adverse drug effects in humans is critical to avoid long-lasting harm. However, current approaches for early detection of adverse effects still lack predictive and organ-specific biomarkers to evaluate undesired responses in humans. Microphysiological systems (MPSs) are in vitro representations of human tissues and provide organ-specific translational insights for physiological processes. In this study, a brain MPS was utilized to assess molecular signatures of neurotoxic and non-neurotoxic compounds using targeted and untargeted molecular approaches. The brain MPS comprising of human embryonic stem (ES) cell-derived neural progenitor cells seeded on three-dimensional (3D), chemically defined, polyethylene glycol hydrogels was treated with the neurotoxic drug, bortezomib and the non-neurotoxic drug, tamoxifen over 14-days. Possible toxic effects were monitored with human N-acetylaspartic acid (NAA) kinetics, which correlates the neuronal function/health and DJ-1/PARK7, an oxidative stress biomarker. Changes in NAA levels were observed as early as 2-days post-bortezomib treatment, while onset detection of oxidative stress (DJ-1) was delayed until 4-days post-treatment. Separately, the untargeted extracellular metabolomics approach revealed distinct fingerprints 2-days post-bortezomib treatment as perturbations in cysteine and glycerophospholipid metabolic pathways. These results suggest accumulation of reactive oxygen species associated with oxidative stress, and disruption of membrane structure and integrity. The NAA response was strongly correlated with changes in a subset of the detected metabolites at the same time point 2-days post-treatment. Moreover, these metabolite changes correlated strongly with DJ-1 levels measured at the later time point (4-days post-treatment). This suggests that early cellular metabolic dysfunction leads to later DJ-1 leakage and cell death, and that early measurement of this subset of metabolites could predict the later occurrence of cell death. While the approach demonstrated here provides an individual case study for proof of concept, we suggest that this approach can be extended for preclinical toxicity screening and biomarker discovery studies.

Impact of the Consciousness Energy Healing-based Novel Test Formulation on Human Organ Specific Biomarkers

Impact of the Consciousness Energy Healing-based Novel Test Formulation on Human Organ Specific Biomarkers

Investigation of Vital Organ Specific Biomarkers Using CellBased Assays after Treatment with the Biofield Energy Treated Test Formulation

Investigation of Vital Organ Specific Biomarkers Using CellBased Assays after Treatment with the Biofield Energy Treated Test Formulation

Comparison of Biodosimetry Biomarkers for Radiation Dose and Injury Assessment After Mixed-Field (Neutron and Gamma) and Pure Gamma Radiation in the Mouse Total-Body Irradiation Model.

The detonation of a nuclear weapon and the occurrence of a nuclear accident represent possible mass-casualty events with significant exposure to mixed neutron and gamma radiation fields in the first few minutes after the event with the ensuing fallout, extending for miles from the epicenter, that would result primarily in photon (gamma- and/or x-ray) exposure. Circulating biomarkers represent a crucial source of information in a mass-casualty radiation exposure triage scenario. We evaluated multiple blood biodosimetry and organ-specific biomarkers for early-response assessment of radiation exposure using a mouse (B6D2F1, males and females) total-body irradiation model exposed to Co gamma rays over a broad dose range (3-12 Gy) and dose rates of either 0.6 or 1.9 Gy min and compared the results with those obtained after exposure of mice to a mixed field (neutrons and gamma rays) using the Armed Forces Radiobiology Research Institute Co gamma-ray source and TRIGA Mark F nuclear research reactor. The mixed-field studies were performed previously over a broad dose range (1.5-6 Gy), with dose rates of either 0.6 or 1.9 Gy min, and using different proportions of neutrons and gammas: either (67% neutrons + 33% gammas) or (30% neutrons + 70% gammas). Blood was collected 1, 2, 4, and 7 d after total-body irradiation. Results from Co gamma-ray studies demonstrate: (1) significant dose- and time-dependent reductions in circulating mature hematopoietic cells; (2) dose- and time-dependent changes in fms-related tyrosine kinase 3 ligand, interleukins IL-5, IL-10, IL-12, and IL-18, granulocyte colony-stimulating factors, thrombopoietin, erythropoietin, acute-phase proteins (serum amyloid A and lipopolysaccharide binding protein), surface plasma neutrophil (CD45) and lymphocyte (CD27) markers, ratio of CD45 to CD27, procalcitonin but not in intestinal fatty acid binding protein; (3) no significant differences were observed between dose-rate groups in hematological and protein profiles (fms-related tyrosine kinase 3 ligand, IL-5, IL-12, IL-18, erythropoietin, granulocyte colony-stimulating factor, granulocyte-macrophage colony-stimulating factor, CD27, CD45, and ratio of CD45 to CD27) for any radiation dose at any time after exposure (p > 0.148); (4) no significant differences were observed between sex groups in hematological and protein profiles (fms-related tyrosine kinase 3 ligand, IL-18, erythropoietin, granulocyte colony-stimulating factor, granulocyte-macrophage colony-stimulating factor, serum amyloid A, CD45) for any radiation dose at any time after exposure (p > 0.114); and (5) PCT level significantly increased (p < 0.008) in mice irradiated with 12 Gy on day 7 post-total-body irradiation without significant differences between groups irradiated at dose rates of either 0.6 or 1.9 Gy min (p > 0.287). Radiation-quality comparison results demonstrate that: (1) equivalent doses of pure gamma rays and mixed-field radiation do not produce equivalent biological effects, and hematopoietic syndrome occurs at lower doses of mixed-field radiation; (2) ratios of hematological and protein biomarker means in the Co study compared to mixed-field studies using 2× Co doses vs. 1× TRIGA radiation doses (i.e., 3 Gy Co vs. 1.5 Gy TRIGA) ranged from roughly 0.2 to as high as 26.5 but 57% of all ratios fell within 0.7 and 1.3; and (3) in general, biomarker results are in agreement with the relative biological effectiveness = 1.95 (Dn/Dt = 0.67) reported earlier by Armed Forces Radiobiology Research Institute scientists in mouse survival countermeasure studies.

Biomarkers for Radiation Biodosimetry and Injury Assessment after Mixed-field (Neutron and Gamma) Radiation in the Mouse Total-body Irradiation Model.

The risk of potential radiation exposure scenarios that include detonation of nuclear weapons, terrorist attacks on nuclear reactors, and the use of conventional explosives to disperse radioactive substances has increased in recent years. The majority of radiation biodosimetry and countermeasure studies have been performed using photon radiation even though many exposure scenarios predict mixed-field (neutron and photon) radiation. Hence, there is a need to evaluate biomarkers and accurately determine exposure levels of mixed-field combinations of neutrons and photons for an individual. These biomarkers will be critical for biodosimetry triage, treatment, and follow-up visits with such individuals. We evaluated the utility of multiple blood biomarkers for early response assessment of radiation exposure using a mouse (B6D2F1, males and females) total-body irradiation model exposed to a mixed-field (neutrons and gamma rays) using the Armed Forces Radiobiology Research Institute's Mark F nuclear research reactor. Total-body irradiation was given as a single exposure over a dose range from 1.5 to 6 Gy, dose rates of 0.6 and 1.9 Gy min, and different proportions of neutrons and gammas: either (67% neutrons + 33% gammas) or (30% neutrons + 70% gammas). Blood was collected 1, 2, 4, and 7 d after total-body irradiation. Radiation-responsive protein biomarkers were measured using the Meso Scale Diagnostics' high-throughput MULTI-ARRAY plate-format platform (QuickPlex 120 Imager) and enzyme-linked immunosorbent assay kits. Results demonstrate (1) dose- and time-dependent changes in fms-related tyrosine kinase 3 ligand, interleukins IL-5, IL-10, IL-12, and IL-18, granulocyte and granulocyte-macrophage colony-stimulating factors, thrombopoietin, erythropoietin, acute-phase proteins (serum amyloid A and lipopolysaccharide binding protein), surface plasma neutrophil (CD45) and lymphocyte (CD27) markers, ratio of CD45 to CD27, and procalcitonin; (2) dose- and time-dependent changes in blood cell counts (lymphocytes, neutrophils, platelets, red blood cells, and ratio of neutrophils to lymphocytes); (3) levels of IL-18, granulocyte and granulocyte-macrophage colony-stimulating factors, serum amyloid A, and procalcitonin were significantly higher in animals irradiated with 67% neutrons + 33% gammas compared to those irradiated with 30% neutrons + 70% gammas (p < 0.015), while no significant differences (p > 0.114) were observed in hematological biomarker counts; (4) exposure with 3-fold difference in dose rate (0.6 or 1.9 Gy min) revealed no significant differences in hematological and protein biomarker levels (p > 0.154); and (5) no significant differences in hematological and protein biomarker levels were observed in the sex-comparison study for any radiation dose at any time after exposure (p > 0.088). Results show that the dynamic changes in the levels of selected hematopoietic cytokines, organ-specific biomarkers, and acute-phase protein biomarkers reflect the time course and severity of acute radiation syndrome and may function as prognostic indicators of acute radiation syndrome outcome. These studies supplement an ongoing effort to deliver U.S. Federal Drug Administration-approved biodosimetry capabilities, which assess mixed-field radiation exposure.

A Host Proteome Atlas of Streptococcus pyogenes Infection.

Multiplex quantitative proteomics analysis of mice infected with Group A Streptococcus reveals organ-specific biomarkers of infection.

Biomarkers in Stable Coronary Artery Disease.

Coronary Artery Disease (CAD) is the most common reason for death in the western hemisphere. Therefore, a well-functioning risk-management has been established over the past decades with uprising interest in 'novel' biomarkers to predict adverse coronary events and detect patients with subclinical CAD. This review will focus on selected biomarkers belonging to the family of inflammatory markers (fibrinogen or hs-CRP) or to the family of lipid-associated markers (Lipoprotein associated PA2 or Lipoprotein a) and organ-specific biomarkers (hs-troponin, Cystatin C or NTproBNP). This review is based on a pubmed search focusing on the biomarkers fibrinogen, hs-CRP, Lipoprotein associated PA2, Lipoprotein a, hs-troponin, NT-proBNP and Cystatin C. The search retrieved 149 references containing meta-analysis, prospective and retrospective studies concerning the usage of the selected biomarkers in risk prediction and detection of CAD. Despite clinical studies, current guidelines of the European Society of Cardiology (ESC), the American Heart Association (AHA) and the Canadian Cardiovascular Society (CCS) were analyzed regarding their recommendation of the implementation of biomarkers in clinical routine. The review identified promising stand-alone biomarkers and multi-marker risk models for CAD patients. Novel biomarkers detect patients at risk beyond established risk scores. However, an ideal biomarker fulfilling all necessary criteria does still not exist.

Organ-specific biomarkers in lupus.

Systemic lupus erythematosus (SLE) is a complex and highly heterogeneous disease, which affects multiple organs, including joints, skin, kidneys, heart, hematopoietic system, and nerve system. While the etiopathogenesis of SLE still remains unclear, genetic susceptibilities and aberrant epigenetic modifications are believed to be involved. For precision therapy, it is necessary to assess accurately and objectively organ involvements and disease activity, which is difficult by current clinical laboratory tests. Biomarkers, which are a biologic, genetic, epigenetic or a chemical characteristic and conveniently detectable, serve as measures of disease diagnosis, activity, prognosis, and manifestation prediction, thereby providing instruction for individualized therapy. In addition, biomarkers differ according to different manifestations, since the disease activity index and treatments vary significantly. For example, unlike other non-renal SLE, lupus nephritis requires significant immunosuppressive drugs. Over the past decades, the research on biomarkers in lupus has been strengthened and numerous promising biomarkers have been identified at levels of genomics, transcriptomics and proteomics. In this review, we summarize the conventional and novel biomarkers in the tissue-specific manner, and discuss their roles in specific organ diagnosis, future manifestation prediction, disease activity assessment and their correlation with histology results. By doing so, it aims to shed a light on individualized treatment.

New technologies - new insights into the pathogenesis of hepatic encephalopathy.

Hepatic encephalopathy (HE) is a neuropsychiatric syndrome which frequently accompanies acute or chronic liver disease. It is characterized by a variety of symptoms of different severity such as cognitive deficits and impaired motor functions. Currently, HE is seen as a consequence of a low grade cerebral oedema associated with the formation of cerebral oxidative stress and deranged cerebral oscillatory networks. However, the pathogenesis of HE is still incompletely understood as liver dysfunction triggers exceptionally complex metabolic derangements in the body which need to be investigated by appropriate technologies. This review summarizes technological approaches presented at the ISHEN conference 2014 in London which may help to gain new insights into the pathogenesis of HE. Dynamic in vivo 13C nuclear magnetic resonance spectroscopy was performed to analyse effects of chronic liver failure in rats on brain energy metabolism. By using a genomics approach, microRNA expression changes were identified in plasma of animals with acute liver failure which may be involved in interorgan interactions and which may serve as organ-specific biomarkers for tissue damage during acute liver failure. Genomics were also applied to analyse glutaminase gene polymorphisms in patients with liver cirrhosis indicating that haplotype-dependent glutaminase activity is an important pathogenic factor in HE. Metabonomics represents a promising approach to better understand HE, by capturing the systems level metabolic changes associated with disease in individuals, and enabling monitoring of metabolic phenotypes in real time, over a time course and in response to treatment, to better inform clinical decision making. Targeted fluxomics allow the determination of metabolic reaction rates thereby discriminating metabolite level changes in HE in terms of production, consumption and clearance.

Radiation Metabolomics: Current Status and Future Directions.

Human exposure to ionizing radiation (IR) disrupts normal metabolic processes in cells and organs by inducing complex biological responses that interfere with gene and protein expression. Conventional dosimetry, monitoring of prodromal symptoms, and peripheral lymphocyte counts are of limited value as organ- and tissue-specific biomarkers for personnel exposed to radiation, particularly, weeks or months after exposure. Analysis of metabolites generated in known stress-responsive pathways by molecular profiling helps to predict the physiological status of an individual in response to environmental or genetic perturbations. Thus, a multi-metabolite profile obtained from a high-resolution mass spectrometry-based metabolomics platform offers potential for identification of robust biomarkers to predict radiation toxicity of organs and tissues resulting from exposures to therapeutic or non-therapeutic IR. Here, we review the status of radiation metabolomics and explore applications as a standalone technology, as well as its integration in systems biology, to facilitate a better understanding of the molecular basis of radiation response. Finally, we draw attention to the identification of specific pathways that can be targeted for the development of therapeutics to alleviate or mitigate harmful effects of radiation exposure.