Targeting GluR3 in Depression and Alzheimer's Disease: Novel Compounds and Therapeutic Prospects.

BACKGROUND: The present study investigates the interrelated pathophysiology of depression and Alzheimer's disease (AD), with the objective of elucidating common underlying mechanisms. OBJECTIVE: Our objective is to identify previously undiscovered biogenic compounds from the NuBBE database that specifically interact with GluR3. This study examines the bidirectional association between depression and AD, specifically focusing on the role of depression as a risk factor in the onset and progression of the disease. METHODS: In this study, we utilize pharmacokinetics, homology modeling, and molecular docking-based virtual screening techniques to examine the GluR3 AMPA receptor subunit. RESULTS: The compounds, namely ZINC000002558953, ZINC000001228056, ZINC000000187911, ZINC000003954487, and ZINC000002040988, exhibited favorable pharmacokinetic profiles and drug-like characteristics, displaying high binding affinities to the GluR3 binding pocket. CONCLUSIONS: These findings suggest that targeting GluR3 could hold promise for the development of therapies for depression and AD. Further validation through in vitro, in vivo, and clinical studies is necessary to explore the potential of these compounds as lead candidates for potent and selective GluR3 inhibitors. The shared molecular mechanisms between depression and AD provide an opportunity for novel treatment approaches that address both conditions simultaneously.

Chemically Defined Lactobacillus plantarum Cell-Free Metabolites Demonstrate Cytoprotection in HepG2 Cells through Nrf2-Dependent Mechanism.

Centering around the concept that metabolites from the gut commensals can exert metabolic health benefits along the gut-liver axis, we tested whether the cell-free global metabolome of probiotic bacteria can exert hepatoprotective benefits against H2O2-induced oxidative stress. Cell-free global metabolites of Lactobacillus plantarum (LPM) were isolated and untargeted metabolomics was performed. The free radical scavenging potentials of LPM were measured. The cytoprotective effects of LPM were tested on HepG2 cells. A total of 66 diverse metabolites were identified in LPM, among which saturated fatty acids, amino acids and dicarboxylic acids were highly enriched. LPM attenuated cell damage, lipid peroxidation and the levels of intracellular cytoprotective enzymes in H2O2-treated cells. LPM also attenuated H2O2-induced increased expressions of TNF-α and IL-6. However, the cytoprotective effects of LPM were diminished in cells that were pretreated with a pharmacological inhibitor of Nrf2. Our data collectively indicate that LPM can significantly attenuate oxidative damage to HepG2 cells. However, the cytoprotective effects of LPM likely depend on an Nrf2-dependent mechanism.

Interventions to Increasing Test Cancellation Rates in Blood Bank Based on a Multi-Year Review.

BACKGROUND: Apart from the wasted resource, canceled tests cause delay of test results thus affecting patient care. The study aimed to identify the reasons for the test cancellation of samples received in a blood bank laboratory and determine the improvement target. METHODS: The study retrospectively reviewed the canceled tests in a blood bank laboratory of a hospital in Hail, Saudi Arabia, from January 2017 to December 2020. Records of the canceled test taken from the quality assurance database were utilized to identify the various reasons. RESULTS: A total of 2,017 (2.7%) test cancellations were recorded in the 4-year study period with increasing rates noted. The two primary reasons were specimen quality issues (61.9%) and problems related to test orders (33.9%). The main reason for test cancellation was clotted specimen (48.5%) followed by incorrect test order (15.6%) and duplicate test order (13.9%). Statistically, a significant difference exists between the annual rates and reasons of cancellation, X2 (6, n = 2,017) = 83.24, p < 0.001. CONCLUSIONS: Test cancellations due to various reasons remain a significant challenge for clinical laboratories. Detailed analyses on these major reasons can aid in displaying an effective approach to decrease the cancellation rates. Harmonization among inter-professional health workers concerning specimen collection and handling, and involving clinical laboratory personnel could minimize laboratory errors and avoid test cancellations.

Detecting Preanalytical Errors Using Quality Indicators in a Hematology Laboratory.

BACKGROUND AND OBJECTIVES: Monitoring laboratory performance continuously is crucial for recognizing errors and fostering further improvements in laboratory medicine. This study aimed to review the quality indicators (QIs) and describe the laboratory errors in the preanalytical phase of hematology testing in a clinical laboratory. METHODS: All samples received in the Hematology Laboratory of the Maternity and Pediatric Hospital in Hail for 3 years were retrospectively reviewed and evaluated for preanalytical issues using a set of QIs. The rate of each QI was compared to the quality specifications cited in the literature. RESULTS: A total of 95002 blood samples were collected for analysis in the hematology laboratory from January 2017 through December 2019. Overall, 8852 (9.3%) were considered to show preanalytical errors. The most common were "clotted specimen" (3.6%) and "samples not received" (3.5%). Based on the quality specifications, the preanalytical QIs were classified generally as low and medium level of performance. In contrast, the sigma-based performance level indicates acceptable performance on all the key processes. Further analysis of the study showed a decreasing rate of preanalytical errors from 11.6% to 6.5%. CONCLUSIONS: Preanalytical errors remain a challenge to hematology laboratories. The errors in this case were predominantly related to specimen collection procedures that compromised the specimen quality. Quality indicators are a valuable instrument in the preanalytical phase that allows an opportunity to improve and explore clinical laboratory process performance and progress. Continual monitoring and management of QI data are critical to ensure ongoing satisfactory performance and to enhance the quality in the preanalytical phase.

Anaerosalibacter bizertensis gen. nov., sp. nov., a halotolerant bacterium isolated from sludge.

A strictly anaerobic, halotolerant and thermotolerant strain, designated C5BEL(T), was isolated in north Tunisia from storage tanks holding waste generated by the recycling of discarded motor oils. Cells of strain C5BEL(T) were Gram-stain-positive, motile by laterally inserted flagella, straight, and spore-forming. Their two major fatty acids were iso-C(15 : 0) and iso-C(15 : 0) dimethyl acetal. Growth was observed at temperatures of 25-55 °C (optimum, 40 °C) and at pH 6-9 (optimum, pH 7.5). The salinity range for growth was 0-100 g l(-1) NaCl (optimum, 5 g l(-1)). Yeast extract was required for growth. Strain C5BEL(T) was heterotrophic, able to use glucose, pyruvate, succinate, yeast extract, bio-trypticase and peptone, but unable to grow on Casamino acids. Sulfate, thiosulfate, sulfite, elemental sulfur, fumarate, nitrate and nitrite were not reduced. The DNA G+C content of strain C5BEL(T) was 31.1 mol%. 16S rRNA gene sequence analysis indicated that strain C5BEL(T) was a member of the family Clostridiaceae, class Clostridia, phylum Firmicutes and was most closely related to Sporanaerobacter acetigenes Lup33(T) ( = DSM 13106(T)) (92.4 % similarity). On the basis of 16S rRNA gene sequence comparisons and physiological characteristics, strain C5BEL(T) can be classified as a novel species in a new genus, for which the name Anaerosalibacter bizertensis gen. nov., sp. nov. is proposed. The type strain of the type species is C5BEL(T) ( = DSM 23801(T) = JCM 17239(T)).

Sporosalibacterium faouarense gen. nov., sp. nov., a moderately halophilic bacterium isolated from oil-contaminated soil.

A novel strictly anaerobic, moderately halophilic and mesophilic bacterium, designated strain SOL3f37(T), was isolated from a hydrocarbon-polluted soil surrounding a deep petroleum environment located in south Tunisia. Cells of strain SOL3f37(T) stained Gram-positive and were motile, straight and spore-forming. Strain SOL3f37(T) had a typical Gram-positive-type cell-wall structure, unlike the thick, multilayered cell wall of its closest relative Clostridiisalibacter paucivorans. The major fatty acids were iso-C(15 : 0) (41 %), iso-C(14 : 0) 3-OH and/or iso-C(15 : 0) dimethyl acetal (21.6 %), iso-C(13 : 0) (4.4 %), anteiso-C(15 : 0) (3.9 %) and iso-C(15 : 1) (2.8 %). Strain SOL3f37(T) grew between 20 and 48 °C (optimum 40 °C) and at pH 6.2-8.1 (optimum pH 6.9). Strain SOL3f37(T) required at least 0.5 NaCl l(-1) and grew in the presence of NaCl concentrations up to 150 g l(-1) (optimum 40 g l(-1)). Yeast extract (2 g l(-1)) was required for degradation of pyruvate, fumarate, fructose, glucose and mannitol. Also, strain SOL3f37(T) grew heterotrophically on yeast extract, peptone and bio-Trypticase, but was unable to grow on Casamino acids. Sulfate, thiosulfate, sulfite, elemental sulfur, fumarate, nitrate and nitrite were not reduced. The DNA G+C content was 30.7 mol%. Phylogenetic analysis based on 16S rRNA gene sequences revealed that strain SOL3f37(T) was a member of the family Clostridiaceae in the order Clostridiales; strain SOL3f37(T) was related to members of various genera of the family Clostridiaceae. It exhibited highest 16S rRNA gene sequence similarity (93.4 %) with Clostridiisalibacter paucivorans 37HS60(T), 91.8 % with Thermohalobacter berrensis CTT3(T) and 91.7 % with Caloranaerobacter azorensis MV1087(T). On the basis of genotypic, phenotypic and phylogenetic data, it is suggested that strain SOL3f37(T) represents a novel species in a new genus. The name Sporosalibacterium faouarense gen. nov., sp. nov. is proposed, with SOL3f37(T) (=DSM 21485(T) =JCM 15487(T)) as the type strain of Sporosalibacterium faouarense.