Autophagy regulates the maturation of hematopoietic precursors in the embryo

An understanding of the mechanisms regulating embryonic hematopoietic stem cell (HSC) development would facilitate their regeneration. The aorta-gonad-mesonephros region is the site for HSC production from hemogenic endothelial cells (HEC). While several distinct regulators are involved in this process, it is not yet known whether macroautophagy (autophagy) plays a role in hematopoiesis in the pre-liver stage. Here, we show that different states of autophagy exist in hematopoietic precursors and correlate with hematopoietic potential based on the LC3-RFP-EGFP mouse model. Deficiency of autophagy-related gene 5 (Atg5) specifically in endothelial cells disrupts endothelial to hematopoietic transition (EHT), by blocking the autophagic process. Using combined approaches, including single-cell RNA-sequencing (scRNA-seq), we have confirmed that Atg5 deletion interrupts developmental temporal order of EHT to further affect the pre-HSC I maturation, and that autophagy influences hemogenic potential of HEC and the formation of pre-HSC I likely via the nucleolin pathway. These findings demonstrate a role for autophagy in the formation/maturation of hematopoietic precursors.</p

Transforming Growth Factor beta 1 Gene Play a Novel Role in Innate Immune Response in Pelteobagrus fulvidraco

Transforming growth factor-beta 1 (TGF-beta 1) as a member of TGF-beta superfamily plays crucial roles in regulation of immune responses. Yellow catfish, Pelteobagrus fulvidraco, is one of the most important freshwater aquaculture species in China, but little is known about its genes related to immune response. The present study cloned cDNA encoding TGF-beta 1 from P. fulvidraco. The results showed the full-length cDNA of TGF-beta 1 is 2,816 bp and encodes 461 amino acids. The homology of P. fulvidraco TGF-beta 1 depicted 83% and 81% similarity to the TGF-beta 1 in Stegastes partitus and Pundamilia nyererei respectively. The phylogenetic tree construction revealed that P. fulvidraco is closely related to Astyanax mexicanus. Analysis of mRNA expression of TGF-beta 1 in different tissues (gonads, brain, liver, kidney, spleen, intestine, blood, gills, muscle and heart) revealed that TGF-beta 1 is predominantly expressed in liver and brain, followed by gill and spleen. TGF-beta 1 gene in gill and spleen up-regulated for 48h after Edwardsiella ictaluri and Flavobacterium columnare injection, then the expression showed a significant decrease (p&lt;0.05). These results indicated that TGF-beta 1 contributes to the inherent immune reaction of P. fulvidraco

Selenium-Containing Polysaccharide-Protein Complex in Se-Enriched Ulva fasciata Induces Mitochondria-Mediated Apoptosis in A549 Human Lung Cancer Cells

The role of selenium (Se) and Ulva fasciata as potent cancer chemopreventive and chemotherapeutic agents has been supported by epidemiological, preclinical, and clinical studies. In this study, Se-containing polysaccharide-protein complex (Se-PPC), a novel organoselenium compound, a Se-containing polysaccharide-protein complex in Se-enriched Ulva fasciata, is a potent anti-proliferative agent against human lung cancer A549 cells. Se-PPC markedly inhibited the growth of cancer cells via induction of apoptosis which was accompanied by the formation of apoptotic bodies, an increase in the population of apoptotic sub-G1 phase cells, upregulation of p53, and activation of caspase-3 in A549 cells. Further investigation on intracellular mechanisms indicated that cytochrome C was released from mitochondria into cytosol in A549 cells after Se-PPC treatment. Se-PPC induced depletion of mitochondrial membrane potential (ΔΨm) in A549 cells through regulating the expression of anti-apoptotic (Bcl-2, Bcl-XL) and pro-apoptotic (Bax, Bid) proteins, resulting in disruption of the activation of caspase-9. This is the first report to demonstrate the cytotoxic effect of Se-PPC on human cancer cells and to provide a possible mechanism for this activity. Thus, Se-PPC is a promising novel organoselenium compound with potential to treat human cancers

Protection of Siganus oramin, rabbitfish, from heavy metal toxicity by the selenium-enriched seaweed Gracilaria lemaneiformis

Seaweed is an inherently important entity in marine ecosystems. It is not only consumed by aquatic animals but also improves environmental quality in the mariculture. Seaweed is also part of the diet of human beings. The purpose of the present study was to evaluate the antagonism of selenium (Se)-enriched Gracilaria lemaneiformis against heavy metals, specifically, the potential of dietary Se-enriched Gracilaria to protect against heavy metal toxicity in rabbitfish (Siganus oramin). Growth rate, heavy metal (Se, Cd, Pb, Cu, Zn and Cr) concentrations, malondialdehyde (MDA), metallothionein (MT), and the activity of the antioxidants, glutathione peroxidase (GPX), catalase (CAT) and superoxide dismutase (SOD) were all assessed. The results showed that the total organic and inorganic Se concentration for the 250 mg L-1 Se-enriched Gracilaria was significantly higher than those of the 50 and 10 mg L-1 treatments after 3 days of enrichment. The mean total Se concentrations in Gracilaria were 42.5 mu g g(-1)- in the 250 mg L-1 treatment, 13.5 mu g g(-1)- in the 50 mg L-1 treatment and 2.5 mu g g(-1) in the 10 mg L-1 treatment, respectively. Organic Se accounts for 80-82% of total Se in Se-enriched Gracilaria. The Se concentration of rabbitfish fed Se-enriched Gracilaria was significantly higher than control. Furthermore, Se increased Cu and Zn absorption, and enhanced MT generation, and improved GPX, CAT, and SOD antioxidant activity, and decreased MDA concentrations and lipid pemxidation levels, all antagonistic to Cd, Pb and Cr. The effects of Se-enriched Gracilaria on waterborne Cd, Pb and Cr-induced toxicity occurred via both enzymatic and non-enzymatic antioxidative mechanisms in rabbitfish. Selenium had synergistic effects on Zn and Cu in rabbitfish. For the 50 mg L-1 Se-enriched Gracilaria treatment, the Se, Cu, Zn, and antagonistic Cd, Pb, Cr, and the antioxidant enzymes CAT, SOD, GPX activities, and MT concentrations in rabbitfish were higher than that with the 250 mg L-1 and 10 mg L-1 Se-enriched Gracilaria treatments. The 50 mg L-1 Se treatment of Gracilaria was deemed to be the optimum concentration to promote growth of rabbitfish. Therefore, the obtained results suggest Se-enriched Gracilaria can antagonize heavy metal toxicity, and is an advisable Se supplement to improve the edible safety of cultured animals

Potential bioremediation effects of seaweed Gracilaria lemaneiformis on heavy metals in coastal sediment from a typical mariculture zone

Seaweeds are good bio-monitors of heavy metals pollution in coastal seawater. In the present study, the potential bioremediation effects of cultivated Gracilaria lemaneiformis on heavy metals in Nan'ao coastal sediment from a typical mariculture zone, South China were evaluated. Sediment samples were collected from five different zones (Gracilaria cultivation zone, G; Fish culture zone, F; Shellfish culture zone, S; Transition zone, T; Control zone, C) from December 2014 to July 2015. The concentrations of Cd, Pb, Cu, and Zn in the sediments were significantly different among the various types of mariculture areas. The concentrations varied widely: Cd (0.04-1.02) mu g g(-1); Cu (1.19-37.70) mu g g(-1); Pb (8.45-74.45) mu g g(-1); Zn (36.80-201.24) mu g g(-1). The lowest heavy metal concentrations in the sediment were occurred at Gracilaria cultivation zone, while higher concentrations occurred at control zones and fish culture zones. The pollution load index, principal components and cluster analysis showed that heavy metal concentrations were the highest at fish culture zone, while the concentrations were the lowest at Gracilaria cultivation zone, and Gracilaria cultivation affects the heavy metals in the sediments. Gracilaria had strong adsorption capacities for heavy metals from seawater, showing the highest heavy metal Bioconcentration Factors in May (higher seaweed biomass period). Consequently, the results suggested that Gracilaria cultivation influences the heavy metal concentrations in sediments from the typical coastal mariculture zone. Gracilaria cultivation has the potential to bioremediate heavy metals in the coastal sediments. Therefore, Gracilaria cultivation can add environmental advantages and ecological values to coastal mariculture zones. (C) 2019 Elsevier Ltd. All rights reserved

Protection of dietary selenium-enriched seaweed Gracilaria lemaneiformis against cadmium toxicity to abalone Haliotis discus hannai

Seaweed Gracilaria lemaneiformis is the main dietary source of the abalone mariculture industry in China. In this study, we examined the protection of selenium (Se)-enriched G. lemaneiformis against cadmium (Cd) toxicity in the abalone, Haliotis discus hannai, using various indices including metal concentration (Se and Cd), growth rate, GPx enzymatic antioxidants, and metallothionein (MT) concentration over a period of 28 days of exposure. The growth rates and Se contents increased significantly in abalones fed with Se-enriched G. lemaneiformis, while the toxicity of Cd was reduced. Seven to 12 days Cd exposure to the Se-enriched G. lemaneiformis not only affected GPx activity but the MT levels fluctuated irregularly. MT concentrations increased after 3 days exposure and then gradually decreased to the control level after Day 7. There were statistically significant positive correlations between MT levels, GPx activity and Se concentrations, and negative relationships between MT levels, GPx activity and Cd levels in abalones. These findings suggest that Se-enriched Gracilaria protects abalone against Cd toxicity. The possible mechanism is the induction of MT with a concomitant increased capacity of GPx enzymatic antioxidants

Gene microarray analysis revealed a potential crucial gene RACK1 in oral squamous cell carcinoma (OSCC)

Oral squamous cell carcinoma (OSCC) is the sixth most common cancer worldwide, which appears as a consequence of multiple molecular genetic events in various chromosomes and genes. In order to unveil the possible mechanisms underlying OSCC tumorigenesis, the OSCC-related gene expression variance and the gene interaction network should be further investigated. Herein, we conducted the NimbleGen Human Gene Expression Microarray to analyze expression heterogeneity between OSCC primary tumor tissue and its adjacent normal tissue from two patients. A total number of 7872 out of 32,448 detected genes are differentially expressed in OSCC. Gene ontology (GO) analysis demonstrated that these differentially expressed transcripts were critical in a series of metabolic processes, cancer-related signal pathways, and biological regulations. KEGG signaling pathway enrichment suggested a number of pathways (metabolic process and immune response) which are frequently enrolled during cancer progression. 15 most differential regulated genes between OSCC tumor and non-tumor were confirmed by quantitative reverse transcription polymerase chain reaction (qRT-PCR). Furthermore, the interaction network analysis of these confirmed genes by STRING database showed the two subunits of RACK1 had direct interaction with 14 differential proteins. This bioinformatics research lends support about the critical role of RACK1 which functions as a key node protein driving OSCC development

Short-term exposure to antibiotics begets long-term disturbance in gut microbial metabolism and molecular ecological networks

Abstract Background Antibiotic exposure can occur in medical settings and from environmental sources. Long-term effects of brief antibiotic exposure in early life are largely unknown. Results Post a short-term treatment by ceftriaxone to C57BL/6 mice in early life, a 14-month observation was performed using 16S rRNA gene-sequencing technique, metabolomics analysis, and metagenomics analysis on the effects of ceftriaxone exposure. Firstly, the results showed that antibiotic pre-treatment significantly disturbed gut microbial α and β diversities (P < 0.05). Both Chao1 indices and Shannon indices manifested recovery trends over time, but they didn’t entirely recover to the baseline of control throughout the experiment. Secondly, antibiotic pre-treatment reduced the complexity of gut molecular ecological networks (MENs). Various network parameters were affected and manifested recovery trends over time with different degrees, such as nodes (P < 0.001, R 2 = 0.6563), links (P < 0.01, R 2 = 0.4543), number of modules (P = 0.0672, R 2 = 0.2523), relative modularity (P = 0.6714, R 2 = 0.0155), number of keystones (P = 0.1003, R 2 = 0.2090), robustness_random (P = 0.79, R 2 = 0.0063), and vulnerability (P = 0.0528, R 2 = 0.28). The network parameters didn't entirely recover. Antibiotic exposure obviously reduced the number of key species in gut MENs. Interestingly, new keystones appeared during the recovery process of network complexity. Changes in network stability might be caused by variations in network complexity, which supports the ecological theory that complexity begets stability. Besides, the metabolism profiles of the antibiotic group and control were significantly different. Correlation analysis showed that antibiotic-induced differences in gut microbial metabolism were related to MEN changes. Antibiotic exposure also caused long-term effects on gut microbial functional networks in mice. Conclusions These results suggest that short-term antibiotic exposure in early life will cause long-term negative impacts on gut microbial diversity, MENs, and microbial metabolism. Therefore, great concern should be raised about children’s brief exposure to antibiotics if the results observed in mice are applicable to humans. Video Abstrac

Artificial intelligence for non-mass breast lesions detection and classification on ultrasound images: a comparative study

Abstract Background This retrospective study aims to validate the effectiveness of artificial intelligence (AI) to detect and classify non-mass breast lesions (NMLs) on ultrasound (US) images. Methods A total of 228 patients with NMLs and 596 volunteers without breast lesions on US images were enrolled in the study from January 2020 to December 2022. The pathological results served as the gold standard for NMLs. Two AI models were developed to accurately detect and classify NMLs on US images, including DenseNet121_448 and MobileNet_448. To evaluate and compare the diagnostic performance of AI models, the area under the curve (AUC), accuracy, specificity and sensitivity was employed. Results A total of 228 NMLs patients confirmed by postoperative pathology with 870 US images and 596 volunteers with 1003 US images were enrolled. In the detection experiment, the MobileNet_448 achieved the good performance in the testing set, with the AUC, accuracy, sensitivity, and specificity were 0.999 (95%CI: 0.997-1.000),96.5%,96.9% and 96.1%, respectively. It was no statistically significant compared to DenseNet121_448. In the classification experiment, the MobileNet_448 model achieved the highest diagnostic performance in the testing set, with the AUC, accuracy, sensitivity, and specificity were 0.837 (95%CI: 0.990-1.000), 70.5%, 80.3% and 74.6%, respectively. Conclusions This study suggests that the AI models, particularly MobileNet_448, can effectively detect and classify NMLs in US images. This technique has the potential to improve early diagnostic accuracy for NMLs