Differential Effect of Antioxidants Glutathione and Vitamin C on the Hepatic Injuries Induced by Plasmodium berghei ANKA Infection

Malaria is a life-threatening disease caused by Plasmodium and represents one of the main public health problems in the world. Among alterations associated with the disease, we highlight the hepatic impairment resulting from the generation of oxidative stress. Studies demonstrate that liver injuries caused by Plasmodium infection are associated with unbalance of the antioxidant system in hepatocytes, although little is known about the role of antioxidant molecules such as glutathione and vitamin C in the evolution of the disease and in the liver injury. To evaluate disease complications, murine models emerge as a valuable tool due to their similarities between the infectious species for human and mice. Herein, the aim of this study is to evaluate the effect of antioxidants glutathione and vitamin C on the evolution of murine malaria and in the liver damage caused by Plasmodium berghei ANKA infection. Mice were inoculated with parasitized erythrocytes and treated with glutathione and vitamin C, separately, both at 8 mg/kg during 7 consecutive days. Our data showed that during Plasmodium infection, treatment with glutathione promoted significant decrease in the survival of infected mice, accelerating the disease severity. However, treatment with vitamin C promoted an improvement in the clinical outcomes and prolonged the survival curve of infected animals. We also showed that glutathione promoted increase in the parasitemia rate of Plasmodium-infected animals, although treatment with vitamin C has induced significant decrease in parasitemia rates. Furthermore, histological analysis and enzyme biochemical measurement showed that treatment with glutathione exacerbates liver damage while treatment with vitamin C mitigates the hepatic injury induced by the infection. In summary, the current study provided evidences that antioxidant molecules could differently modulate the outcome of malaria disease; while glutathione aggravated the disease outcome and liver injury, the treatment with vitamin C protects the liver from damage and the evolution of the condition.

Associations of Hormonal Biomarkers With Mental Health and Healthy Behaviors Among Mothers of Very-Low-Birthweight Infants

Objectives: To examine the concurrent use of self-report questionnaires and hormonal biomarkers, specifically levels of testosterone and cortisol, along with demographic variables and corrected age (CA) in the assessment of mental health and healthy behaviors among mothers of very-low-birthweight (VLBW, BW < 1,500 g) infants at five time points over 2 years post birth. Method: Data on 40 mothers from a neonatal intensive care unit of a tertiary medical center in the southeast United States were collected from the medical record, standard questionnaires for the mother (depressive symptoms, perceived stress, anxiety, mental health status, parenting stress, and healthy lifestyle behaviors), and biochemical measurement of maternal testosterone and cortisol using enzyme immunoassay at birth, 40 weeks’ postmenstrual age, and 6, 12, and 24 months CA. Results: Maternal self-report of mental health improved from birth to 6 or 12 months then worsened at 24 months. Mixed linear models showed that mothers with higher testosterone levels had more depressive symptoms and smoked more, whereas mothers with higher cortisol levels had healthier behaviors and exercised more. Testosterone levels were negatively correlated with cortisol levels. Marital status, education, and health insurance were the most predictive demographic variables for the levels of hormonal biomarkers, mental health, and healthy behaviors. Conclusions: The use of self-report and biochemical measurement was effective in assessing maternal mental health and healthy behaviors over 2 years post birth, when mothers of VLBW infants tend to experience more mental health problems and parenting difficulties than mothers of normal-BW full-term infants.

Therapeutic Effects of TianDiJingWan on the Aβ25–35-Induced Alzheimer’s Disease Model Rats

The main purpose of this study was to demonstrate the therapeutic effects and mechanism of TDJW, a modern Chinese medicine prescription developed based on the basic traditional Chinese medicine theory of “tonifying the kidney essence,” on the Aβ25–35-induced AD rats. The AD model was established by the intracerebroventricular administrations of Aβ25–35into the hippocampus CA1 tissue of SD male rats. 72 rats were randomly divided into six groups: sham operation, AD model, donepezil, high TDJW group, medium TDJW group, and low TDJW group. After oral administration of TDJW, the results of Morris water maze and step-down test showed that the learning and memory abilities of AD rats were significantly improved. And biochemical measurement demonstrated that Ach and Glu in hippocampus tissues of AD rats were increased as well. Moreover, the Aβdeposits and p-Tau aggregations in hippocampus CA1 tissues of AD rats were attenuated as observed in the micrographs of immunohistochemistry study, and the results of ELISA indicated that the expressions of TNF-α, IL-1β, and IL-6 in hippocampus tissues were significantly decreased. In conclusion, the present study demonstrated that TDJW could be used as a promising therapeutic agent for the clinical applications of AD treatment in patients.

Updating the OMERACT Filter: Implications for Imaging and Soluble Biomarkers

Objective.The Outcome Measures in Rheumatology (OMERACT) Filter provides a framework for the validation of outcome measures for use in rheumatology clinical research. However, imaging and biochemical measures may face additional validation challenges because of their technical nature. The Imaging and Soluble Biomarker Session at OMERACT 11 aimed to provide a guide for the iterative development of an imaging or biochemical measurement instrument so it can be used in therapeutic assessment.Methods.A hierarchical structure was proposed, reflecting 3 dimensions needed for validating an imaging or biochemical measurement instrument: outcome domain(s), study setting, and performance of the instrument. Movement along the axes in any dimension reflects increasing validation. For a given test instrument, the 3-axis structure assesses the extent to which the instrument is a validated measure for the chosen domain, whether it assesses a patient-centered or disease-centered variable, and whether its technical performance is adequate in the context of its application. Some currently used imaging and soluble biomarkers for rheumatoid arthritis, spondyloarthritis, and knee osteoarthritis were then evaluated using the original OMERACT Filter and the newly proposed structure. Breakout groups critically reviewed the extent to which the candidate biomarkers complied with the proposed stepwise approach, as a way of examining the utility of the proposed 3-dimensional structure.Results.Although there was a broad acceptance of the value of the proposed structure in general, some areas for improvement were suggested including clarification of criteria for achieving a certain level of validation and how to deal with extension of the structure to areas beyond clinical trials.Conclusion.General support was obtained for a proposed tri-axis structure to assess validation of imaging and soluble biomarkers; nevertheless, additional work is required to better evaluate its place within the OMERACT Filter 2.0.

Preclinical evaluation of human secretoglobin 3A2 in mouse models of lung development and fibrosis

Secretoglobin (SCGB) 3A2 is a member of the SCGB gene superfamily of small secreted proteins, predominantly expressed in lung airways. We hypothesize that human SCGB3A2 may exhibit anti-inflammatory, growth factor, and antifibrotic activities and be of clinical utility. Recombinant human SCGB3A2 was expressed, purified, and biochemically characterized as a first step to its development as a therapeutic agent in clinical settings. Human SCGB3A2, as well as mouse SCGB3A2, readily formed a dimer in solution and exhibited novel phospholipase A2 inhibitory activity. This is the first demonstration of any quantitative biochemical measurement for the evaluation of SCGB3A2 protein. In the mouse as an experimental animal, human SCGB3A2 exhibited growth factor activity by promoting embryonic lung development in both ex vivo and in vivo systems and antifibrotic activity in the bleomycin-induced lung fibrosis model. The results suggested that human SCGB3A2 can function as a growth factor and an antifibrotic agent in humans. When SCGB3A2 was administered to pregnant female mice through the tail vein, the protein was detected in the dam's serum and lung, as well as the placenta, amniotic fluids, and embryonic lungs at 10 min postadministration, suggesting that SCGB3A2 readily crosses the placenta. The results warrant further development of recombinant SCGB3A2 as a therapeutic agent in treating patients suffering from lung diseases or preterm infants with respiratory distress.

Potential Positive Effects of Pesticides Application on Sesamia inferens (Walker) (Lepidoptera: Insecta)

In China, the pink stem borer (PSB) Sesamia inferens (Walker) (Lepidoptera: Noctuidae) has become a rice pest in some rice-producing regions. The cause of this shift from secondary to major pest is unknown. The major purpose of this study was to examine the effect of five commonly used pesticides in rice fields on reproduction of PSB and on biochemical substances of rice plants. The results showed that the weight of pupae developed from 1st instar larvae treated with 2 mg/L triazophos and the number of eggs laid by emerged females from the treatment were significantly greater than those of the control, increasing by 26.2% and 47%, respectively. In addition, a nontarget insecticide, pymetrozine 100 mg/L, and a target insecticide, chlorantraniliprole 2 mg/L, stimulated reproduction of PSB. Biochemical measurement showed that foliar sprays of these pesticides resulted in significant reductions of contents of resistant substances, flavonoids and phenolic acids, in rice plants. For example, flavonoids and phenolic acids of rice plants treated with triazophos reduced by 48.5% and 22.4%, respectively, compared to the control. Therefore, we predicted that the application of some pesticides, eg triazophos and chlorantraniliprole, may be the cause of the increase in the population numbers of PSB in rice fields.