Antioxidant defense plays a crucial role in the response of an organism to pollutants. Several processes stimulate the production of free radicals or deplete the antioxidant defense, which if not ...regulated properly, may cause oxidative stress in the organisms, leading to damage in DNA, proteins or lipids. Free radicals are also beneficial as it plays an important role in defense against infectious agents, and signal transduction. Hence a delicate balance between antioxidants and free radicals is required. Oxidative stress biomarkers are very useful in disease etiology and environmental toxicological studies. The increase in anthropogenic activities and environmental awareness has resulted in an explosive increase of research in the field of oxidative stress. Snails are excellent organisms for environmental biomonitoring and contribute a major proportion of the invertebrate biomass. In our article, we have summarized the research carried out using glutathione S-transferase (GST), catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GPx), and lipid peroxidation (LPO) in snails exposed to various toxicants and their implication in the environmental monitoring programs. In the end, we have discussed different factors affecting the variations in oxidative biomarkers response for a better understanding of the phenomenon.
DNA damage and oxidative stress in marine gastropod Morula granulata was measured after in vivo exposure to four different concentrations (10, 25, 50, and 100 μg/L) of phenanthrene. Comet assay was ...used for measurement of DNA damage, whereas oxidative stress was assessed using a battery of biomarkers such as glutathione-S-transferase (GST), catalase (CAT), and lipid peroxidation (LPO). Our data showed concentration-dependent increase in percentage DNA in tail (TDNA), LPO, and GST activity in gastropods exposed to phenanthrene. CAT activity in gastropods was not found to be consistent with the phenanthrene concentrations. Significant increase in TDNA was observed at all concentrations above 10 μg/L of phenanthrene. Positive correlations were observed among oxidative stress biomarker and TDNA. Integrated biomarker response (IBR) analysis showed that among the four biomarkers, LPO and DNA damage (TDNA) were the most sensitive in response to phenanthrene exposure. Our results clearly showed that phenanthrene is genotoxic to gastropods and also causes oxidative stress.
Aims
The aim of this study was to screen endophytic fungi isolated from Vinca rosea for their potential to produce acetylcholinesterase (AChE) inhibitors.
Method and Results
Endophytic fungi isolated ...from V. rosea (Catharanthus roseus), were screened for AChE inhibitor production using Ellman's method. Maximum inhibition against AChE (78%) was observed in an isolate VS‐10, identified to be Alternaria alternata on morphological and molecular basis. The isolate also inhibited butyrylcholinesterase (73%). Significant increase (1·3 fold) was achieved after optimization of process parameters using one variable at time approach. The inhibitor was purified using chromatographic techniques. The structure elucidation of the inhibitor was carried out using spectroscopic techniques and was identified to be ‘altenuene’. The purified inhibitor possessed antioxidant potential as revealed by dot blot assay. The insecticidal potential of purified inhibitor was evaluated by feeding Spodoptora litura on diet amended with inhibitor. It evinced significant larval mortality.
Conclusions
Endophytic A. alternata can serve as a source of dual cholinesterase inhibitor ‘altenuene’ with significant antioxidant and insecticidal activity. This is the first report on acetylcholinestearse inhibitory activity of altenuene.
Significance and Impact of the Study
Alternaria alternata has the potential to produce a dual ChE inhibitor with antioxidant activity useful in the treatment of neurodegenerative disorders and in agriculture as biocontrol agent.
The network connection within the car, the "Controller Area Network" (CAN) bus serves as an alternative protocol for electric automobiles. Tragically, the lack of a data authentication technique in ...the CAN bus protocol makes it susceptible to several types of assaults, making it easier for attackers to infiltrate the network. The CAN dataset is collected and the collected datasets attains for preprocessing stage using z-score normalization. For feature extraction, a restricted boltzmann machine (RBM) is used to extract the data. Next, our proposed method (MCFO-DANN) is used to identify and mitigate CAN Bus attacks in electric vehicles. Evaluation against other CAN bus anomaly detection methods demonstrates the superiority of MCFO-DANN, exhibiting higher accuracy. This proactive security solution fortifies electric vehicles against cyber-threats, ensuring real-time monitoring and response, thereby preserving the integrity and safety of the CAN Bus network in electric automobiles.
Background Eosinophilic esophagitis (EoE) is a clinicopathologic entity of increasing worldwide prevalence. IL-5 is essential for eosinophil trafficking, and anti–IL-5 therapy decreases esophageal ...eosinophilia. EoE is associated with prominent mast cell infiltration. Objective We investigated whether anti–IL-5 (mepolizumab) treatment reduced esophageal mast cell accumulation in biopsy specimens from pediatric patients with EoE from a previous randomized anti–IL-5 trial. Methods A subanalysis was completed for children treated with 0.55, 2.5, or 10 mg/kg mepolizumab monthly for 12 weeks followed by no treatment until week 24. Quantitative immunochemistry was used to assess the numbers of eosinophils, tryptase-positive mast cells, IL-9+ cells, and mast cell–eosinophil couplets before and after treatment. Results Forty-three biopsy specimens had adequate tissue for paired analysis. Forty percent of subjects responded to anti–IL-5 (defined as <15 eosinophils per high-power field hpf after mepolizumab therapy), and 77% of all subjects had decreased numbers of mast cells after anti–IL-5. In responders epithelial mast cell numbers decreased from 62 to 19 per hpf ( P < .001), were significantly lower than in nonresponders after therapy ( P < .05), and correlated with eosinophil numbers ( r = 0.75, P < .0001). Mast cells and eosinophils were found in couplets before therapy, and these were significantly decreased only in responders after anti–IL-5 ( P < .001). Esophageal eosinophils comprised the majority of cells that made the mast cell growth factor IL-9. IL-9+ cell numbers decreased from 102 to 71 per hpf ( P < .001) after anti–IL-5. Conclusions Pediatric patients with EoE had significantly fewer mast cells, IL-9+ cells, and mast cell–eosinophil couplets in the esophageal epithelium after anti–IL-5 therapy. Because eosinophils were one source of IL-9, they might support esophageal mastocytosis.
Abstract Limbic endocannabinoid signaling is known to be sensitive to chronic stress; however, studies investigating the impact of prolonged exposure to glucocorticoid hormones have been limited by ...the concurrent exposure to the stress of daily injections. The present study was designed to examine the effects of a noninvasive approach to alter plasma corticosterone (CORT) on the endocannabinoid system. More precisely, we explored the effects of a 4-week exposure to CORT dissolved in the drinking water of mice (100 μg/ml) and measured cannabinoid CB1 receptor binding, endocannabinoid content, activity of the endocannabinoid degrading enzyme fatty acid amide hydrolase (FAAH), and mRNA expression of both the CB1 receptor and FAAH in both the hippocampus and amygdala. Our data demonstrate that CORT decreases CB1 receptor binding site density in both the hippocampus and amygdala and also reduced anandamide (AEA) content and increased FAAH activity within both structures. These changes in both CB1 receptor binding and FAAH activity were not accompanied by changes in mRNA expression of either the CB1 receptor or FAAH in either brain region. Interestingly, our CORT delivery regimen significantly increased 2-AG concentrations within the hippocampus, but not the amygdala. Collectively, these data demonstrate that the confounder of injection stress is sufficient to conceal the ability of protracted exposure to glucocorticoids to reduce CB1 receptor density and augment AEA metabolism within limbic structures. This article is part of a Special Issue entitled: Stress, Emotional Behavior and the Endocannabinoid System.
Critical periods are temporary windows of heightened neural plasticity early in development. For example, fear memories in juvenile rodents are subject to erasure following extinction training, while ...after closure of this critical period, extinction training only temporarily and weakly suppresses fear memories. Persistence of fear memories is important for survival, but the inability to effectively adapt to the trauma is a characteristic of post-traumatic stress disorder (PTSD). We examined whether Nogo Receptor 1 (NgR1) regulates the plasticity associated with fear extinction. The loss of NgR1 function in adulthood eliminates spontaneous fear recovery and fear renewal, with a restoration of fear reacquisition rate equal to that of naive mice; thus, mimicking the phenotype observed in juvenile rodents. Regional gene disruption demonstrates that NgR1 expression is required in both the basolateral amygdala (BLA) and infralimbic (IL) cortex to prevent fear erasure. NgR1 expression by parvalbumin expressing interneurons is essential for limiting extinction-dependent plasticity. NgR1 gene deletion enhances anatomical changes of inhibitory synapse markers after extinction training. Thus, NgR1 robustly inhibits elimination of fear expression in the adult brain and could serve as a therapeutic target for anxiety disorders, such as PTSD.
We report the triton (t) production in midrapidity (|y|<0.5) Au+Au collisions at sqrts_{NN}=7.7-200 GeV measured by the STAR experiment from the first phase of the beam energy scan at the ...Relativistic Heavy Ion Collider. The nuclear compound yield ratio (N_{t}×N_{p}/N_{d}^{2}), which is predicted to be sensitive to the fluctuation of local neutron density, is observed to decrease monotonically with increasing charged-particle multiplicity (dN_{ch}/dη) and follows a scaling behavior. The dN_{ch}/dη dependence of the yield ratio is compared to calculations from coalescence and thermal models. Enhancements in the yield ratios relative to the coalescence baseline are observed in the 0%-10% most central collisions at 19.6 and 27 GeV, with a significance of 2.3σ and 3.4σ, respectively, giving a combined significance of 4.1σ. The enhancements are not observed in peripheral collisions or model calculations without critical fluctuation, and decreases with a smaller p_{T} acceptance. The physics implications of these results on the QCD phase structure and the production mechanism of light nuclei in heavy-ion collisions are discussed.
Blood molecular profiling of circulating tumor cells (CTCs) can enable monitoring of patients with metastatic melanoma during checkpoint inhibitor immunotherapy (CII) and in combination with targeted ...therapies. We developed a microfluidics-based CTC platform to explore CTC profiling utility in CII-treated patients with melanoma using a melanoma messenger RNA (mRNA)/DNA biomarker panel.
Blood samples (n = 213) were collected prospectively from 75 American Joint Committee on Cancer-staged III/IV melanoma patients during CII treatment and those enriched for CTCs. CTC profiling was performed using 5 known melanoma mRNA biomarkers and BRAF V600E DNA mutation. CTC biomarker status associations with clinical outcomes were assessed.
CTCs were detected in 88% of blood samples from patients with melanoma. CTC-derived biomarkers and clinical variables analyzed using classification and regression tree analysis revealed that a combination of lactate dehydrogenase, CTC-mRNA biomarkers, and tumor BRAF-mutation status was indicative of clinical outcomes for patients with stage IV melanoma (n = 52). The panel stratified low-risk and high-risk patients, whereby the latter had poor disease-free (
= 0.03) and overall survival (
= 0.02). Incorporation of a DNA biomarker with mRNA profiling increased overall CTC-detection capability by 57% compared to mRNA profiling only. RNA sequencing of isolated CTCs identified significant catenin beta 1 (
) overexpression (
<0.01) compared to nondisease donor blood. CTC-
was associated with progressive disease/stable disease compared to complete-responder patient status (
= 0.02). Serial CTC profiling identified subclinical disease in patients who developed progressive disease during treatment/follow-up.
CTC-derived mRNA/DNA biomarkers have utility for monitoring CII, targeted, and combinatorial therapies in metastatic melanoma patients.
Gene expression profiling (GEP) has stratified diffuse large B-cell lymphoma (DLBCL) into molecular subgroups that correspond to different stages of lymphocyte development-namely germinal center ...B-cell like and activated B-cell like. This classification has prognostic significance, but GEP is expensive and not readily applicable into daily practice, which has lead to immunohistochemical algorithms proposed as a surrogate for GEP analysis. We assembled tissue microarrays from 475 de novo DLBCL patients who were treated with rituximab-CHOP chemotherapy. All cases were successfully profiled by GEP on formalin-fixed, paraffin-embedded tissue samples. Sections were stained with antibodies reactive with CD10, GCET1, FOXP1, MUM1 and BCL6 and cases were classified following a rationale of sequential steps of differentiation of B cells. Cutoffs for each marker were obtained using receiver-operating characteristic curves, obviating the need for any arbitrary method. An algorithm based on the expression of CD10, FOXP1 and BCL6 was developed that had a simpler structure than other recently proposed algorithms and 92.6% concordance with GEP. In multivariate analysis, both the International Prognostic Index and our proposed algorithm were significant independent predictors of progression-free and overall survival. In conclusion, this algorithm effectively predicts prognosis of DLBCL patients matching GEP subgroups in the era of rituximab therapy.
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