Reserpine (RES), a Vesicular Monoamine Transporter 2 (VMAT2) inhibitor agent, has been used in preclinical research for many years to create animal models for depression and to test experimental ...antidepressant strategies. Nevertheless, evidence of the potential use and validity of RES as a chronic pharmacological model for depression is lacking, and there are no comprehensive studies of the behavioral effects in conjunction with molecular outcomes.
Experiment 1. Following baseline behavior testing sensitive to depression-like phenotype and locomotion (Phase 1), 27 Sprague-Dawley (SD) rats received i.p. either vehicle solution (0.0 mg/kg), low (0.2 mg/kg) or high (0.8 mg/kg) RES dose for 20 days using a pre-determined schedule and reassessed for behavioral phenotypes (Phase 2). After 10 days washout period, and a final behavioral assessment (Phase 3), the brains were collected 16 days after the last injection for mRNA-expression assessment. Experiment 2. In a similar timetable as in Experiment 1 but without the behavioral testing, 12 SD rats underwent repetitive dopamine D2/3 receptor PET scanning with 18FDMFP following each Phase. The binding potential (BPND) of 18FDMFP was quantified by kinetic analysis as a marker of striatal D2/3R availability. Weight and welfare were monitored throughout the study.
Significant, dose-dependent weight loss and behavioral deficits including both motor (hypo-locomotion) and non-motor behavior (anhedonia, mild anxiety and reduced exploration) were found for both the low and high dose groups with significant decrease in D2R mRNA expression in the accumbal region for the low RES group after Phase 3. Both RES treated groups showed substantial increase in 18FDMFP BPND (in line with dopamine depletion) during Phase 2 and 3 compared to baseline and Controls.
The longitudinal design of the study demonstrated that chronic RES administration induced striatal dopamine depletion that persisted even after the wash-out period. However, the behavior phenotype observed were transient. The data suggest that RES administration can induce a rodent model for depression with mild face validity.
•Reduced body-weight and mild/ transient phenotype induced by chronic Reserpine.•Decreased accumbal D2R mRNA and synaptic dopamine post wash-out period.•Reserpine administration showed mild face validity as model of depression.
The XV. Banff conference for allograft pathology was held in conjunction with the annual meeting of the American Society for Histocompatibility and Immunogenetics in Pittsburgh, PA (USA) and focused ...on refining recent updates to the classification, advances from the Banff working groups, and standardization of molecular diagnostics. This report on kidney transplant pathology details clarifications and refinements to the criteria for chronic active (CA) T cell–mediated rejection (TCMR), borderline, and antibody‐mediated rejection (ABMR). The main focus of kidney sessions was on how to address biopsies meeting criteria for CA TCMR plus borderline or acute TCMR. Recent studies on the clinical impact of borderline infiltrates were also presented to clarify whether the threshold for interstitial inflammation in diagnosis of borderline should be i0 or i1. Sessions on ABMR focused on biopsies showing microvascular inflammation in the absence of C4d staining or detectable donor‐specific antibodies; the potential value of molecular diagnostics in such cases and recommendations for use of the latter in the setting of solid organ transplantation are presented in the accompanying meeting report. Finally, several speakers discussed the capabilities of artificial intelligence and the potential for use of machine learning algorithms in diagnosis and personalized therapeutics in solid organ transplantation.
This report focuses on the clarification of the criteria for chronic active T cell–mediated rejection and antibody‐mediated rejection and the optimization of the inflammation threshold for the diagnosis of borderline for acute T cell–mediated rejection, and discusses the potential to use machine learning in diagnostics and personalized therapeutics in solid organ transplantation.
This research assessed the anti-inflammatory and hepatoprotective properties of inosine and the associated mechanism. Inosine pretreatment significantly reduced the secretion of several inflammatory ...factors and serum alanine transaminase (ALT) and aspartate amino transferase (AST) levels in a dose-dependent manner compared with the lipopolysaccharide (LPS) group. In LPS-treated mice, inosine pretreatment significantly reduced the ALT and malondialdehyde (MDA) concentration and significantly elevated the antioxidant enzyme activity. Furthermore, inosine pretreatment significantly altered the relative abundance of the genera, Bifidobacterium, Lachnospiraceae UCG-006, and Muribaculum. Correlation analysis showed that Bifidobacterium and Lachnospiraceae UCG-006 were positively related to the cecal short-chain fatty acids but negatively related to the serum IL-6 and hepatic AST and ALT levels. Notably, inosine pretreatment significantly modulated the hepatic TLR4, MYD88, NF-κB, iNOS, COX2, AMPK, Nfr2, and IκB-α expression. These results suggested that inosine pretreatment alters the intestinal microbiota structure and improves LPS-induced acute liver damage and inflammation through modulating the TLR4/NF-κB signaling pathway.
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•Spirulina platensis polysaccharides (SPLP) had significant hypolipidemic and hypoglycemic effects in HFD-fed rats.•SPLP intervention modulate the hepatic steatosis and mRNA ...expressions involved in lipid and carbohydrate metabolism.•SPLP altered the relative abundance of cecal short-chain fatty acids.•SPLP significantly modulated the intestinal microbiota dysbiosis.
This study aimed to evaluate the possibility that Spirulina platensis crude polysaccharides may ameliorate the lipid and carbohydrate metabolism disorder, including obesity, hyperlipidemia, hyperglycemia, hepatic steatosis, and gut dysbiosis. The results showed Spirulina platensis crude polysaccharides could improve body weight, serum/liver lipid and carbohydrate indexes, and liver antioxidant parameters in high-sucrose and high-fat diet (HFD)-fed rats, which were accompanied by regulated liver mRNA expressions involved in lipid and carbohydrate metabolism disorder. In addition, SPLP intervention significantly decreased cecal level of propionic acid in HFD-fed rats. Notably, the SPLP could alter the relative abundance of Firmicutes, Bacteroides, Proteobacteria, and Actinobacteria at phylum levels. Based on Spearman's rank correlation coefficient, serum/liver lipid and carbohydrate profiles were found significantly positively correlated with genera Romboutsia, Allobaculum, Blautia, Phascolarctobacterium, Bifidobacterium, Coprococcus, Turicibacter, Erysipelotrichaceae_unclassified, Olsenella, Escherichia/Shigella, Coprobacillus, Lachnospiracea incertae, and Lactobacillus, but strongly negatively correlated with genera Atopostipes, Flavonifractor, Porphyromonadaceae_unclassified, Barnesiella, Oscillibacter, Paraprevotella, Jeotgalicoccus, Corynebacterium, Alloprevotella and Bacteroides. It was concluded that oral administration of SPLP could remarkably ameliorate the lipid and carbohydrate metabolism disorder and significantly modulate the intestinal microbiota in HFD-fed rats.
The present study aimed to (1) investigate biocompatibility and cytotoxicity of pulp-capping materials on viability of human dental pulp stem cells (hDPSCs); (2) determine angiogenic, odontogenic, ...and osteogenic marker mRNA expressions; and (3) observe changes in surface morphology of the hDPSCs using scanning electron microscopy (SEM).
Impacted third molars were used to isolate the hDPSCs, which were treated with extract-release fluids of the pulp-capping materials (Harvard BioCal-Cap, NeoPUTTY MTA, TheraCal LC, and Dycal). Effects of the capping materials on cell viability were assessed using 3-(4,5-di-methyl-thiazol-2-yl)-5-(3-carboxy-methoxy-phenyl)-2-(4-sulfo-phenyl)-2H-tetrazolium (MTS) assay and the apoptotic/necrotic cell ratios and reactive oxygen species (ROS) levels from flow cytometry. Marker expressions (alkaline phosphatase ALP, osteocalcin OCN, collagen type I alpha 1 Col1A, secreted protein acidic and rich in cysteine SPARC, osteonectin ON, and vascular endothelial growth factor VEGF) were determined by quantitative reverse-transcription polymerase chain reaction. Changes in surface morphology of the hDPSCs were visualised by SEM.
The MTS assay results at days 1, 3, 5, and 7 indicated that Harvard BioCal-Cap, NeoPUTTY MTA, and TheraCal LC did not adversely affect cell viability when compared with the control group. According to the MTS assay results at day 14, no significant difference was found amongst Dycal, Harvard BioCal-Cap, NeoPUTTY MTA, and TheraCal LC affecting cell viability. Dycal was the only capping material that increased ROS level. High levels of VEGF expression were observed with Harvard BioCal-Cap, TheraCal LC, and NeoPUTTY MTA. NeoPUTTY MTA, and Dycal upregulated OCN expression, whereas TheraCal LC upregulated Col1A and SPARC expression. Only Dycal increased ALP expression. HDSCs were visualized in characteristic spindle morphology on SEM when treated with TheraCal LC and Harvard BioCal-Cap.
NeoPUTTY MTA and Harvard BioCal-Cap showed suitable biocompatibility values; in particular, these pulp-capping materials were observed to support the angiogenic marker.
Bisphenol S (BPS) is increasingly used in a wide range of industrial and consumer products, resulting in its ubiquitous distribution across the environment, including aquatic ecosystems. Although it ...is commonly known as a weak/moderate estrogenic compound, there has been a growing acknowledgment of the potential of BPS to cause toxicity by inducing oxidative stress. Oxidative stress is a major participant in the development of anxiety-like behaviors in humans and animals. Therefore, the present study was designed to examine the impact of BPS on anxiety-like behavior and fear responses in adult zebrafish and also to elucidate the possible linkage between the BPS neurotoxicity and oxidative status of the brain. To this end, adult male and female zebrafish were exposed to 0 (control), 1, 10, and 30 μg/L of BPS and 1 μg/L of 17-β-estradiol (E2) for 75 days. Following exposure, changes in anxiety and fear-related responses were evaluated by applying a novel tank test and by exposing focal fish to chemical alarm cues. Additionally, we evaluated the expression of multiple antioxidant genes in the zebrafish brain. Our results indicate that BPS, irrespective of exposure concentration, and E2 significantly decreased bottom-dwelling behavior and the latency to enter the upper water column. Furthermore, exposure to the highest concentration of BPS and E2 induced a significant decrease in fear-related responses. The impaired anxiety and reduced fear-related responses were associated with a down-regulation in the transcription of genes involved in enzymatic antioxidant defense. Taken together, our results suggest that chronic exposure to BPS impairs anxiety and fear responses in adult zebrafish, possibly by inducing oxidative stress in the brain.
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•Exposure to bisphenol S and estradiol impaired anxiety response in zebrafish.•High concentration of bisphenol S impaired fear response in zebrafish.•BPS and estradiol altered the expression of the enzymatic antioxidant defense genes.•Impaired anxiety and fear responses were associated with dysfunction of antioxidant defense system.
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•• A major new insect transcriptomics web resource for Tribolium castaneum.•• View RNAseq data for adult and larval tissues, and different embryonic stages.•• Query by gene, tissue ...and function, or retrieve genes with similar patterns of expression.•• Use both Drosophila and Tribolium gene identifiers for searches.•• Gene results link out to tissue expression tables of beetle paralogues and fly homologues.
The red flour beetle Tribolium castaneum has emerged as a powerful model in insect functional genomics. However, a major limitation in the field is the lack of a detailed spatio-temporal view of the genetic signatures underpinning the function of distinct tissues and life stages. Here, we present an ontogenetic and tissue-specific web-based resource for Tribolium transcriptomics: BeetleAtlas (https://www.beetleatlas.org). This web application provides access to a database populated with quantitative expression data for nine adult and seven larval tissues, as well as for four embryonic stages of Tribolium. BeetleAtlas allows one to search for individual Tribolium genes to obtain values of both total gene expression and enrichment in different tissues, together with data for individual isoforms. To facilitate cross-species studies, one can also use Drosophila melanogaster gene identifiers to search for related Tribolium genes. For retrieved genes there are options to identify and display the tissue expression of related Tribolium genes or homologous Drosophila genes. Five additional search modes are available to find genes conforming to any of the following criteria: exhibiting high expression in a particular tissue; showing significant differences in expression between larva and adult; having a peak of expression at a specific stage of embryonic development; belonging to a particular functional category; and displaying a pattern of tissue expression similar to that of a query gene. We illustrate how the different feaures of BeetleAtlas can be used to illuminate our understanding of the genetic mechanisms underpinning the biology of what is the largest animal group on earth.
Membrane-associated ring-CH-type finger 1 (MARCH1), which mediates the ubiquitination of CD86 and MHC class II proteins, plays crucial roles in ruminant fecundity. To completely explore the functions ...of MARCH1 in goat reproduction, the mRNA expression of this gene were investigated in different tissues of goats. Moreover, we analyzed the association of three insertions and deletions (indels) within MARCH1 with litter size in a large population of Shaanbei white cashmere goats (n = 2844). It showed that MARCH1 was expressed in all examined tissues, including the spleen, brain, lungs, liver, muscles, and testis, of 14- and 56-day-old male goats and in the ovary tissues of female goats. However, MARCH1 expression levels in the testis and lungs were significantly different between the 14- and 56-day-old male goats. Therefore, we examined MARCH1 expression levels in the testis of male goats belonging to different developmental age groups, i.e., 0-, 14-, 28-, 42-, and 56-day-old male goats. Our results indicated a potential association between MARCH1 expression and mitosis-to-meiosis transition. Furthermore, we identified three novel 7-, 15-, and 18-bp indels in MARCH1 in the Shaanbei white cashmere goat population. The presence of the three indels significantly affected MARCH1 expression in the testis and ovary. Statistical analyses indicated that these indels were associated with first-born litter size (P < 0.05). A significant difference was observed in the genotype distribution of the three indels between single- and multi-lamb female goats (P < 0.05). Together, these findings suggest that MARCH1 plays a crucial role in fertility and that the three novel indels in the goat MARCH1 can be used as effective molecular markers for marker-assisted selection of goats for breeding in the future.
•The expression levels of MARCH1 in mitosis period was significantly higher than that in meiosis period in testis.•Three novel indels within MARCH1 were associated with goat first-born litter size.•Three novel indels may affect the function of MARCH1 by impacting the expression levels.
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