GT 949

Effect of Camellia sinensis on Fat Peroxidation and Ox-LDL in Rats

Green tea (GT) is believed to have antioxidant properties and beneficial effects on the treatment of some diseases. However, few findings were found concerning the impact of GT on oxidative stress. In the present study, the protective influence of GT against the oxidative stress caused by hydrogen peroxide (H2O2) in rats was evaluated. The research groups included a control (Con) group and five groups supplemented with 10g GT(G1), 20g GT(G2), 1% H2O2(P), 1% H2O2and10g GT (GP1), as well as 1% H2O2 and 20g GT(GP2). The effects of GT and H2O2 administration on serum biochemical parameters, such as lipid profile, malondialdehyde (MDA), and oxidized low-density lipoprotein (Ox-LDL) were assessed. The findings of this research revealed that the usage of GT lowered the level of cholesterol, triglyceride, LDL, MDA, Ox-LDL and coronary risk index. Moreover, an increase in high-density lipoprotein and very-low-density lipoprotein (VLDL) was observed in subjects who received GT, compared to the rats of the P group. The baseline lipid profile and GT consumption with or without H2O2 were the same between the Con and GT-treated groups. Therefore, GT usage was found to be advantageous in reducing Ox-LDL and lipid peroxidation in rats. These results confirm the traditionally claimed benefits of GT for protection against lipid peroxidation and atherosclerosis.

Chr21 protein-protein interactions: enrichment in proteins involved in intellectual disability, autism, and late-onset Alzheimer's disease

Down syndrome (DS) is caused by human chromosome 21 (HSA21) trisomy. It is characterized by a poorly understood intellectual disability (ID). We studied two mouse models of DS, one with an extra copy of the <i>Dyrk1A</i> gene (189N3) and the other with an extra copy of the mouse Chr16 syntenic region (Dp(16)1Yey). RNA-seq analysis of the transcripts deregulated in the embryonic hippocampus revealed an enrichment in genes associated with chromatin for the 189N3 model, and synapses for the Dp(16)1Yey model. A large-scale yeast two-hybrid screen (82 different screens, including 72 HSA21 baits and 10 rebounds) of a human brain library containing at least 10<sup>7</sup> independent fragments identified 1,949 novel protein-protein interactions. The direct interactors of HSA21 baits and rebounds were significantly enriched in ID-related genes (<i>P</i>-value < 2.29 × 10<sup>-8</sup>). Proximity ligation assays showed that some of the proteins encoded by HSA21 were located at the dendritic spine postsynaptic density, in a protein network at the dendritic spine postsynapse. We located HSA21 DYRK1A and DSCAM, mutations of which increase the risk of autism spectrum disorder (ASD) 20-fold, in this postsynaptic network. We found that an intracellular domain of DSCAM bound either DLGs, which are multimeric scaffolds comprising receptors, ion channels and associated signaling proteins, or DYRK1A. The DYRK1A-DSCAM interaction domain is conserved in <i>Drosophila</i> and humans. The postsynaptic network was found to be enriched in proteins associated with ARC-related synaptic plasticity, ASD, and late-onset Alzheimer's disease. These results highlight links between DS and brain diseases with a complex genetic basis.

Decoding the Mechanism of Action of Rapid-Acting Antidepressant Treatment Strategies: Does Gender Matter?

Gender differences play a pivotal role in the pathophysiology and treatment of major depressive disorder. This is strongly supported by a mean 2:1 female-male ratio of depression consistently observed throughout studies in developed nations. Considering the urgent need to tailor individualized treatment strategies to fight depression more efficiently, a more precise understanding of gender-specific aspects in the pathophysiology and treatment of depressive disorders is fundamental. However, current treatment guidelines almost entirely neglect gender as a potentially relevant factor. Similarly, the vast majority of animal experiments analysing antidepressant treatment in rodent models exclusively uses male animals and does not consider gender-specific effects. Based on the growing interest in innovative and rapid-acting treatment approaches in depression, such as the administration of ketamine, its metabolites or electroconvulsive therapy, this review article summarizes the evidence supporting the importance of gender in modulating response to rapid acting antidepressant treatment. We provide an overview on the current state of knowledge and propose a framework for rodent experiments to ultimately decode gender-dependent differences in molecular and behavioural mechanisms involved in shaping treatment response.

Intracranial-Pressure-Monitoring-Assisted Management Associated with Favorable Outcomes in Moderate Traumatic Brain Injury Patients with a GCS of 9-11

Objective: With a mortality rate of 10-30%, a moderate traumatic brain injury (mTBI) is one of the most variable traumas. The indications for intracranial pressure (ICP) monitoring in patients with mTBI and the effects of ICP on patients' outcomes are uncertain. The purpose of this study was to examine the indications of ICP monitoring (ICPm) and its effects on the long-term functional outcomes of mTBI patients.
Methods: Patients with Glasgow Coma Scale (GCS) scores of 9-11 at Tangdu hospital, between January 2015 and December 2021, were enrolled and treated in this retrospective cohort study. We assessed practice variations in ICP interventions using the therapy intensity level (TIL). Six-month mortality and a Glasgow Outcome Scale Extended (GOS-E) score were the main outcomes. The secondary outcome was neurological deterioration (ND) events. The indication and the estimated impact of ICPm on the functional outcome were investigated by using binary regression analyses.
Results: Of the 350 patients, 145 underwent ICP monitoring-assisted management, and the other 205 patients received a standard control based on imaging or clinical examinations. A GCS ≤ 10 (OR 1.751 (95% CI 1.216-3.023), p = 0.003), midline shift (mm) ≥ 2.5 (OR 3.916 (95% CI 2.076-7.386) p < 0.001), and SDH (OR 1.772 (95% CI 1.065-2.949) p = 0.028) were predictors of ICP. Patients who had ICPm (14/145 (9.7%)) had a decreased 6-month mortality rate compared to those who were not monitored (40/205 (19.5%), p = 0.011). ICPm was linked to both improved neurological outcomes at 6 months (OR 0.815 (95% CI 0.712-0.933), p = 0.003) and a lower ND rate (2 = 11.375, p = 0.010). A higher mean ICP (17.32 ± 3.52, t = -6.047, p < 0.001) and a more significant number of ICP > 15 mmHg (27 (9-45.5), Z = -5.406, p < 0.001) or ICP > 20 mmHg (5 (0-23), Z = -4.635, p < 0.001) 72 h after injury were associated with unfavorable outcomes. The best unfavorable GOS-E cutoff value of different ICP characteristics showed that the mean ICP was >15.8 mmHg (AUC 0.698; 95% CI, 0.606-0.789, p < 0.001), the number of ICP > 15 mmHg was >25.5 (AUC 0.681; 95% CI, 0.587-0.774, p < 0.001), and the number of ICP > 20 mmHg was >6 (AUC 0.660; 95% CI, 0.561-0.759, p < 0.001). The total TIL score during the first 72 h post-injury in the non-ICP group (9 (8, 11)) was lower than that of the ICP group (13 (9, 17), Z = -8.388, p < 0.001), and was associated with unfavorable outcomes.
Conclusion: ICPm-assisted management was associated with better clinical outcomes six months after discharge and lower incidences of ND for seven days post-injury. A mean ICP > 15.8 mmHg, the number of ICP > 15 mmHg > 25.5, or the number of ICP > 20 mmHg > 6 implicate an unfavorable long-term prognosis after 72 h of an mTBI.

Antibiotics in Wastewater: Baseline of the Influent and Effluent Streams in Kuwait

This study provides baseline information on the concentrations of antibiotics in influent and effluent from two wastewater treatment plants in regular operation in the State of Kuwait. Wastewater samples were collected from the influent and effluent streams of two WWTPs, over four sampling campaigns and analyzed for a broad range of antibiotics. The mean influent concentrations of sulfamethoxazole, ciprofloxacin, clarithromycin, and cefalexin were 852 ng/L, 672 ng/L, 592 ng/L), and 491 ng/L, respectively, at Umm Al Hayman WWTP. At the Kabd WWTP, the influent concentration of clarithromycin was highest with a mean of 949 ng/L, followed by ciprofloxacin (mean, 865 ng/L), cefalexin (mean, 598 ng/L), and sulfamethoxazole (mean, 520 ng/L). The dominant compounds in the effluent from Umm Al Hayman were sulfamethoxazole (mean, 212 ng/L), ciprofloxacin (mean, 153 ng/L), ofloxacin (mean, 120 ng/L), dimetridazole (mean, 96 ng/L), and metronidazole (mean, 93 ng/L). Whereas, at the Kabd WWTP, the dominant compounds were sulfamethoxazole (mean, 338 ng/L), dimetridazole (mean, 274 ng/L), cefalexin (mean, 213 ng/L), ciprofloxacin (mean, 192 ng/L), and clarithromycin (189 ng/L). The mean influent concentrations of all compounds were higher than those measured in the effluents. The concentrations of antibiotic compounds were not significantly different between the two WWTPs (p > 0.05). The removal efficiencies of the various antibiotics over the four sampling campaigns for the Kabd and Umm Hayman WWTPs ranged between 10.87 and 99.75% and also showed that they were variable and were compound dependent. The data clearly show that the concentrations of antibiotics measured in the influents of both WWTPs were highest in samples collected during the winter-summer (September samples) transition followed by the concentrations measured during the winter-summer (March samples) transition period. This is possibly linked to the increased prescription of these medications to treat infectious diseases and flu prevalent in Kuwait during these periods. This study provides the first reported concentrations of antibiotics in the dissolved aqueous influents and effluents of WWTPs in Kuwait. Additional studies are required to evaluate the environmental impact that antibiotic residues may cause since treated wastewater is used in irrigation, and often there are instances when untreated wastewater is discharged directly into the marine environment.