Dian Wang

Effects of trace element supplementation on the inflammatory response in a rabbit model of major trauma

Patients with a severe trauma exhibit a strong oxidative stress, an intense inflammatory response, and long-lasting hypermetabolism, all of which are proportional to the severity of injury. In this study, we investigated the impact of trace element (TE) supplementation on the inflammatory response in an animal model of major trauma. New Zealand White rabbits were randomly assigned as a control group (n=5) and an experimental group (n=70) that, after receiving a major trauma, was subdivided into Trauma-Control (n=35) and Trauma-TE (n=35) groups. Systemic inflammatory response syndrome (SIRS) was observed in 40 out of 70 rabbits with a trauma, with a higher incidence in the Trauma-Control group (88.6%; 31/35) than the Trauma-TE group (28.6%; 10/35) (p<0.01). The mortality rate was significantly different between the Trauma-Control and the Trauma-TE groups; (34% vs. 8%; p<0.01). There were significant post-trauma alterations in the levels of (1) serum and spleen zinc (Zn), copper (Cu), selenium (Se), and manganese (Mn), (2) serum AST and ALT, (3) serum interleukin-6/10, and (4) nuclear factor kappa binding (NF-kappaB) activity and the expression. TE supplementation: (1) improved blood urea nitrogen (BUN), and creatinine (Cr) levels, (2) stabilized IL-6/10 production, (3) decreased NF-kappaB p(65) production. Appropriate TE supplementation can improve the TE status, mitigate SIRS, and reduce the mortality due to multiple organ dysfunction syndromes (MODS)/multiple organ failure (MOF) after major trauma.

Time of Death Revealed by Hydrocarbons of Empty Puparia of Chrysomya megacephala (Fabricius) (Diptera: Calliphoridae): A Field Experiment

Determination of the postmortem interval (PMI) is crucial for investigating homicide. However, there are currently only limited methods available. Especially, once the PMI exceeds the duration of pre-adult development of the flies with the adult emergence, its determination is very approximate. Herein, we report the regular changes in hydrocarbon composition during the weathering process of the puparia in the field in Chrysomya megacephala (Fabricius) (Diptera: Calliphoridae), one of the common species of necrophagous flies. Correlation analysis showed that the relative abundance of nearly all of the branched alkanes and alkenes decreased significantly with the weathering time. Especially, for 9 of the peaks, over 88% of the variance in their abundance was explained by weathering time. Further analysis indicated that the regular changes caused mainly by the different weathering rates of various hydrocarbons. Additionally, the weathering rates were found to depend on the chemical structure and molecular weight of the hydrocarbons. These results indicate strongly that hydrocarbon analysis is a powerful tool for determining the weathering time of the necrophagous fly puparia, and is expected to markedly improve the determination of the late PMI.

Severe Diffuse Axon Injury in Chronic Alcoholic Rat Medulla Oblongata Following a Concussion Blow

AIMS We investigated the axonal morphological changes and expression of both tau protein and β-APP following concussion to the medulla oblongata, in a rat model of chronic alcoholism. METHODS Fifty-nine male Sprague-Dawley rats were randomly divided into EtOH, EtOH-TBI and control groups (water group, water-TBI group). To establish chronic alcoholic rats, rats were intragastrically given edible spirituous liquor twice daily. Rats also received a blow on the occipital tuberosity with an iron pendulum. Morphological changes and expression of tau and β-APP proteins in the medulla oblongata were examined. RESULTS (a) Nerve fibre thickening and twisting were observed in alcoholic rats, with nerve fibre changes becoming more significant following a concussion blow, which leads to some nerve fibres fracturing. (b) Transmission electron microscopy revealed that the nerve fibre myelin became loosened and displayed lamellar separation, which became more significant following concussion. (c) The integral optical density (IOD) sum value of β-APP of the EtOH-TBI group was lower than that in the EtOH group (P < 0.05); the Tau IOD sum value of the EtOH-TBI group was higher than that in the EtOH group (P < 0.05). CONCLUSION (a) Chronic alcoholism caused nerve fibre and neuronal morphology damage in the rat medulla oblongata, with structural damage becoming more significant following concussion. (b) Concussion changed the expression of β-APP and tau protein in chronic alcoholic rat medulla oblongata, suggesting that chronic alcoholism can lead to severe axonal injury following a concussion blow. (c) The effect of chronic alcoholism may be synergistic the concussion blow to promote animal injury and death.

GC–MS-based metabolomics identifies an amino acid signature of acute ischemic stroke

Ischemic stroke is a serious public health problem worldwide. Here, we characterized the metabolite features of acute ischemic stroke (AIS) using a gas chromatography-mass spectrometry-based metabolomics. Forty AIS patients and 29 sex and age-matched controls were recruited. The serum metabolic profiles were significantly different between the two groups. Compared to the controls, the patients had elevated levels of lactate, carbonate and glutamate (P<0.01), and lowered levels of alanine, citrate, glycine, isoleucine, leucine, serine, tyrosine, methionine, tryptophan, erythronic acid, urea, purine, hypoxanthine, and proline in the serum (P<0.05). Amino acids are the most important disturbed metabolites. Most dysregulated metabolites are closely correlated with each other and with several biochemical indices. The differential metabolites reflect pathophysiological processes of inflammation, energy deficit, oxidative stress, neurotoxicity, neuro excitation and injury. Tyrosine, lactate, and tryptophan were screened as a panel of potential biomarkers of AIS, jointly enabling a high precision (91.7%) to diagnose AIS by classification and regression tree (CRT). Collectively, we discovered a marked perturbation of metabolome of AIS in the serum, mainly associated with amino acid-related metabolism. Tyrosine, lactate, and tryptophan may be considered as potential biomarkers of AIS.

GC-MS-Based metabolomics discovers a shared serum metabolic characteristic among three types of epileptic seizures.

OBJECTIVE Understanding the overall and common metabolic changes of seizures can provide novel clues for their control and prevention. Here, we aim to investigate the global metabolic feature of serum for three types of seizures. METHODS We recruited 27 patients who had experienced a seizure within 48h (including 11 who had a generalized seizure, nine who had a generalized seizure secondary to partial seizure and seven who had a partial seizure) and 23 healthy controls. We analyzed the global metabolic changes of serum after seizures using gas chromatography-mass spectrometry-based metabolomics. Based on differential metabolites, the metabolic pathways and their potential to diagnose seizures were analyzed, and metabolic differences among three types of seizures were compared. RESULTS The metabolic profiles of serum were distinctive between the seizure group and the controls but were not different among the three types of seizures. Compared to the controls, patients with seizures had higher levels of lactate, butanoic acid, proline and glutamate and lower levels of palmitic acid, linoleic acid, elaidic acid, trans-13-octadecenoic acid, stearic acid, citrate, cysteine, glutamine, asparagine, and glyceraldehyde in the serum. Furthermore, these differential metabolites had common change trends among the three types of seizures. Related pathophysiological processes reflected by these metabolites are energy deficit, inflammation, nervous excitation and neurotoxicity. Importantly, transamination inhibition is suspected to occur in seizures. Lactate, glyceraldehyde and trans-13-octadecenoic acid in serum jointly enabled a precision of 92.9% for diagnosing seizures. CONCLUSIONS There is a common metabolic feature in three types of seizures. Lactate, glyceraldehyde and trans-13-octadecenoic acid levels jointly enable high-precision seizure diagnosis.

Metabolic Characterization of Myocardial Infarction Using GC-MS-Based Tissue Metabolomics

Understanding the metabolic features of myocardial infarction (MI) is critical to its prevention and treatment. Here, we aimed to characterize the metabolic features of early MI using a tissue metabolomics method based on gas chromatography-mass spectrometry (GC-MS). Thirty-four pairs of infarcted myocardia and their matched non-infarcted myocardia were collected from 34 rats that underwent coronary artery ligation (CAL); their metabolic profiles were compared by GC-MS-based tissue metabolomics to characterize the metabolic features of MI. On the basis of differential metabolites, their diagnostic potential for MI was analyzed, and MI-related metabolic pathways were investigated. Serum samples before and post MI were used to validate the results obtained in myocardia. The metabolic profile of the infarcted myocardia was obviously different from that of the non-infarcted myocardia, as indicated by partial least squares discriminate analysis (PLS-DA) plots. Twenty-two metabolites were identified to be different between the infarcted myocardia and non-infarcted myocardia. These metabolic alterations reflect energy deficit, acidosis, oxidative stress, ionic imbalance, and cardiac injury post MI. Glutamine, glutamate, and lactate were confirmed to jointly confer a favorable potential for diagnosing MI, which can be well validated in serum.

The densities of visceral organs and the extent of pathologic changes.

In this study, we designed a new device to measure the density of internal organs and correlated with their pathologic changes. The densities of hearts, livers, lungs and brains from 169 autopsy cases were measured with different extent of pathologic changes by an integrated volume-density meter. All samples were divided into 2 groups: intact and pathologic groups. The extent of pathologic changes was classified into 3 stages: slight edema, intermediate edema, severe edema (or severe fatty degeneration only for livers) according to the histologic features. Results show that there were significant differences between each subgroup and intact group and the density was closely correlated with pathologic changes. Therefore, the external parameter of density might offer some clues to its pathologic changes, such as edema and fatty changes.

Pontine Changes in Metabolites and Axonal Fibres of Rats Following Four-week Alcohol Exposure: In Vivo Diffusion Tensor Imaging and 1h-magnetic Resonance Spectroscopy Study at 7.0 T.

Aims We characterized the metabolite content and axonal fibre changes in the rat pontine, in vivo , using 1H-magnetic resonance spectroscopy (1H-MRS) and diffusion tensor imaging (DTI) with a 7.0 T magnetic resonance imaging (MRI) scanner following chronic alcohol administration to explore new indicators for the early diagnosis and treatment of chronic alcoholism. Methods Forty male Sprague-Dawley rats were randomly divided into the EtOH and control groups (water group). To establish a chronic alcohol administration rat model, rats were intragastrically administered edible wine (56% vol/vol) twice daily for four weeks. Quantitation of the changes in metabolite concentrations and the apparent diffusion coefficient (ADC), as well as the fractional anisotropy (FA) values, within the pontine of brain stem were detected using MRS and DTI at 7.0 T. Differences of the pontine metabolite content, ADC and FA values between the two groups were compared. Results The 7.0 T MRIs showed no abnormal T2 phase pontine signals in either the EtOH or control groups. A 1H-MRS scan showed that the values for NAA, Cr and Cho in the EtOH group (4.54 ± 0.69, 4.69 ± 0.70 and 1.32 ± 0.18) were lower than those in the controls (6.78 ± 0.76, 8.50 ± 0.83 and 1.89 ± 0.24) ( P 0.05). DTI showed that the FA value in chronic alcohol exposure rats (0.41 ± 0.12) was lower than the control rats (0.53 ± 0.08) ( P 0.05). Conclusions After chronic alcohol exposure for four weeks, the metabolite content and axonal fibre changes in the rat pontine can be detected using MRS and DTI at 7.0 T earlier than conventional MRI, which provides information for the early diagnosis and treatment of chronic alcoholism. Short Summary In the present study, the authors showed that the metabolite content and axonal fibre changes in the pontine of chronic ethanol-treated rats can be detected using MRS and DTI at 7.0 T earlier than conventional MRI, which provide objective indicators for the early diagnosis and treatment of chronic alcoholism.

Altered Levels of Zinc and N-methyl-D-aspartic Acid Receptor Underlying Multiple Organ Dysfunctions After Severe Trauma

Background Severe trauma can cause secondary multiple organ dysfunction syndrome (MODS) and death. Oxidative stress and/or excitatory neurotoxicity are considered as the final common pathway in nerve cell injuries. Zinc is the cofactor of the redox enzyme, and the effect of the excitatory neurotoxicity is related to N-methyl-D-aspartic acid receptor (NMDAR). Material/Methods We investigated the levels of zinc and brainstem NMDAR in a rabbit model of severe trauma. Zinc and serum biochemical profiles were determined. Immunohistochemistry was used to detect brainstem N-methyl-D-aspartic acid receptor 1 (NR1), N-methyl-D-aspartic acid receptor 2A (NR2A), and N-methyl-D-aspartic acid receptor 2B (NR2B) expression. Results Brain and brainstem Zn levels increased at 12 h, but serum Zn decreased dramatically after the trauma. NR1 in the brainstem dorsal regions increased at 6 h after injury and then decreased. NR2A in the dorsal regions decreased to a plateau at 12 h after trauma. The levels of NR2B were lowest in the death group in the brainstem. Serum zinc was positively correlated with NR2A and 2B and negatively correlated with zinc in the brain. Correlations were also found between the brainstem NR2A and that of the dorsal brainstem, as well as between brainstem NR2A and changes in NR2B. There was a negative correlation between zinc and NR2A. Conclusions Severe trauma led to an acute reduction of zinc enhancing oxidative stress and the changes of NMDAR causing the neurotoxicity of the nerve cells. This may be a mechanism for the occurrence of MODS or death after trauma.

Serum lipid feature and potential biomarkers of lethal ventricular tachyarrhythmia (LVTA) induced by myocardial ion channel diseases: a rat model study.

To determine the cause of death in myocardial ion channel diseases (MICD)-induced sudden cardiac death (SCD) cases is a difficulty in forensic identification practices. The majority of MICD-induced SCD cases would experience lethal ventricular tachyarrhythmia (LVTA) before deaths; thus, confirming the occurrence of LVTA in bodies can offer a key evidence to identify these cases. Several lipids in the myocardia were found disturbed after LVTA; yet, whether serum lipidome would be disrupted by LVTA is not clear. Therefore, we aimed to screen lipid feature and related diagnostic markers of LVTA in serum here. An aconitine-induced LVTA-SCD rat model was produced. Blood samples before LVTA and immediately after LVTA were retrieved and related serum specimens were used for ultra-performance liquid chromatography-mass spectrometry (UPLC-MS)-based lipidomics analyses. On the basis of the defined differential lipids, a lipid-related metabolic pathway network was constructed and potential biomarkers were screened. Twelve aconitine-induced LVTA rats were produced. Totally, 188 lipids in serum were disrupted during the LVTA-SCD process, which belong to 11 lipid classes. Most of the differential lipids were correlated, suggesting that they were interacted and that the changes were holistic during LVTA process. Ten lipid pathways were activated during LVTA process; the main lipid classes involved in these pathways were ceramide, sphingomyelin, phosphatidylcholine, phosphatidylethanolamine, and phosphatidylserine. Phosphatidylcholine O-40:4, sphingomyelin d46:5, and phosphatidylethanolamine 40:4 were tested as potential diagnostic markers of LVTA-SCD event in serum. The current results indicate a substantial change in serum lipidome after LVTA-SCD; lipidomics holds promise to identify MICD-induced SCDs in forensic practices.