ABSTRACT
Inflammatory bowel disease (IBD), including Crohn's disease (CD) and ulcerative colitis (UC), is associated with a loss or an imbalance of host-microorganism interactions. However, such interactions at protein levels remain largely unknown. Here, we applied a depletion-assisted metaproteomics approach to obtain in-depth host-microbiome association networks of IBD, where the core host proteins shifted from those maintaining mucosal homeostasis in controls to those involved in inflammation, proteolysis, and intestinal barrier in IBD. Microbial nodes such as short-chain fatty-acid producer-related host-microbial crosstalk were lost or suppressed by inflammatory proteins in IBD. Guided by protein-protein association networks, we employed proteomics and lipidomics to investigate the effects of UC-related core proteins S100A8, S100A9, and cytokines (IL-1ß, IL-6, and TNF-α) on gut bacteria. These proteins suppressed purine nucleotide biosynthesis in stool-derived in vitro communities, which was also reduced in IBD stool samples. Single species study revealed that S100A8, S100A9, and cytokines can synergistically or antagonistically alter gut bacteria intracellular and secreted proteome, with combined S100A8 and S100A9 potently inhibiting beneficial Bifidobacterium adolescentis. Furthermore, these inflammatory proteins only altered the extracellular but not intracellular proteins of Ruminococcus gnavus. Generally, S100A8 induced more significant bacterial proteome changes than S100A9, IL-1ß, IL-6, and TNF-α but gut bacteria degrade significantly more S100A8 than S100A9 in the presence of both proteins. Among the investigated species, distinct lipid alterations were only observed in Bacteroides vulgatus treated with combined S100A8, S100A9, and cytokines. These results provided a valuable resource of inflammatory protein-centric host-microbial molecular interactions.
Subject(s)
Colitis, Ulcerative , Cytokines , Gastrointestinal Microbiome , Colitis, Ulcerative/microbiology , Colitis, Ulcerative/metabolism , Humans , Cytokines/metabolism , Calgranulin B/metabolism , Calgranulin A/metabolism , Proteomics , Feces/microbiology , Ruminococcus/metabolism , Host Microbial Interactions , ClostridialesABSTRACT
Recently, evidence of aromatic amine antioxidants (AAs) existence in the dust of the electronic waste (e-waste) dismantling area has been exposed. However, there are limited studies investigating occupational exposure and toxicity associated with AAs and their transformation products (p-phenylenediamines-quinones, i.e., PPD-Qs). In this study, 115 dust and 42 hand wipe samples collected from an e-waste recycling industrial park in central China were analyzed for 19 AAs and 6 PPD-Qs. Notably, the median concentration of ∑6PPD-Qs (1,110 ng/g and 1,970 ng/m2) was significantly higher (p < 0.05, Mann-Whitney U test) than that of ∑6PPDs (147 ng/g and 34.0 ng/m2) in dust and hand wipes. Among the detected analytes, 4-phenylaminodiphenylamine quinone (DPPD-Q) (median: 781 ng/g) and 1,4-Bis(2-naphthylamino) benzene quinone (DNPD-Q) (median: 156 ng/g), were particularly prominent, which were first detected in the e-waste dismantling area. Occupational exposure assessments and nuclear receptor interference ability, conducted through estimated daily intake (EDI) and molecular docking analysis, respectively, indicated significant occupational exposure to PPD-Qs and suggested prioritized Liver X receptors (LXRs) disruption potential of PPDs and PPD-Qs. The study provides the first evidence of considerable levels of AAs and PPD-Qs in the e-waste-related hand wipe samples and underscores the importance of assessing occupational exposure and associated toxicity effects.
Subject(s)
Antioxidants , Dust , Electronic Waste , Occupational Exposure , Recycling , Occupational Exposure/analysis , Humans , Dust/analysis , China , Quinones/analysis , Amines/analysisABSTRACT
Mitochondrial genomics, as a useful marker for phylogenetics and systematics of organisms, are important for molecular biology studies. The phylogenetic relationships of the Polypedilum generic complex remains controversial, due to lack taxonomy and molecular information. In this study, we newly sequenced mitogenomes of 14 species of the Polypedilum generic complex. Coupled with three recently published sequences, we analyzed the nucleotide composition, sequence length, and evolutionary rate of this generic complex. The control region showed the highest AT content. The evolution rate of protein coding genes was as follows: ATP8 > ND6 > ND5 > ND3 > ND2 > ND4L > ND4 > COX1 > ND1 > CYTB > APT6 > COX2 > COX3. We reconstructed the phylogenetic relationships among the genera within the Polypedilum generic complex based on 19 mitochondrial genomes (seventeen ingroups and two outgroups), using Bayesian Inference (BI) and Maximum Likelihood (ML) methods for all databases. Phylogenetic analysis of 19 mitochondrial genomes demonstrated that the Endochironomus + Synendotendipes was sister to Phaenopsectra + Sergentia.
ABSTRACT
Gut ecosystem has profound effects on host physiology and health. Gastrointestinal (GI) symptoms were frequently observed in patients with COVID-19. Compared with other organs, gut antiviral response can result in more complicated immune responses because of the interactions between the gut microbiota and host immunity. However, there are still large knowledge gaps in the impact of COVID-19 on gut molecular profiles and commensal microbiome, hindering our comprehensive understanding of the pathogenesis of SARS-CoV-2 and the treatment of COVID-19. We performed longitudinal stool multi-omics profiling to systemically investigate the molecular phenomics alterations of gut ecosystem in COVID-19. Gut proteomes of COVID-19 were characterized by disturbed immune, proteolysis and redox homeostasis. The expression and glycosylation of proteins involved in neutrophil degranulation and migration were suppressed, while those of proteases were upregulated. The variable domains of Ig heavy chains were downregulated and the overall glycosylation of IgA heavy chain constant regions, IgGFc-binding protein, and J chain were suppressed with glycan-specific variations. There was a reduction of beneficial gut bacteria and an enrichment of bacteria derived deleterious metabolites potentially associated with multiple types of diseases (such as ethyl glucuronide). The reduction of Ig heave chain variable domains may contribute to the increase of some Bacteroidetes species. Many bacteria ceramide lipids with a C17-sphingoid based were downregulated in COVID-19. In many cases, the gut phenome did not restore two months after symptom onset. Our study indicates widely disturbed gut molecular profiles which may play a role in the development of symptoms in COVID-19. Our findings also emphasis the need for ongoing investigation of the long-term gut molecular and microbial alterations during COVID-19 recovery process. Considering the gut ecosystem as a potential target could offer a valuable approach in managing the disease.
Subject(s)
COVID-19 , Gastrointestinal Microbiome , Ecosystem , Feces , Humans , SARS-CoV-2ABSTRACT
BACKGROUND: Proteolysis regulation allows gut microbes to respond rapidly to dynamic intestinal environments by fast degradation of misfolded proteins and activation of regulatory proteins. However, alterations of gut microbial proteolytic signatures under complex disease status such as inflammatory bowel disease (IBD, including Crohn's disease (CD) and ulcerative colitis (UC)), have not been investigated. Metaproteomics holds the potential to investigate gut microbial proteolysis because semi-tryptic peptides mainly derive from endogenous proteolysis. RESULTS: We have developed a semi-tryptic peptide centric metaproteomic mining approach to obtain a snapshot of human gut microbial proteolysis signatures. This approach employed a comprehensive meta-database, two-step multiengine database search, and datasets with high-resolution fragmentation spectra to increase the confidence of semi-tryptic peptide identification. The approach was validated by discovering altered proteolysis signatures of Escherichia coli heat shock response. Utilizing two published large-scale metaproteomics datasets containing 623 metaproteomes from 447 fecal and 176 mucosal luminal interface (MLI) samples from IBD patients and healthy individuals, we obtain potential signatures of altered gut microbial proteolysis at taxonomic, functional, and cleavage site motif levels. The functional alterations mainly involved microbial carbohydrate transport and metabolism, oxidative stress, cell motility, protein synthesis, and maturation. Altered microbial proteolysis signatures of CD and UC mainly occurred in terminal ileum and descending colon, respectively. Microbial proteolysis patterns exhibited low correlations with ß-diversity and moderate correlations with microbial protease and chaperones levels, respectively. Human protease inhibitors and immunoglobulins were mainly negatively associated with microbial proteolysis patterns, probably because of the inhibitory effects of these host factors on gut microbial proteolysis events. CONCLUSIONS: This semi-tryptic peptide centric mining strategy offers a label-free approach to discover signatures of in vivo gut microbial proteolysis events if experimental conditions are well controlled. It can also capture in vitro proteolysis signatures to facilitate the evaluation and optimization of experimental conditions. Our findings highlight the complex and diverse proteolytic events of gut microbiome, providing a unique layer of information beyond taxonomic and proteomic abundance. Video abstract.
Subject(s)
Gastrointestinal Microbiome , Peptide Fragments/analysis , Peptide Fragments/metabolism , Proteolysis , Proteomics , Trypsin/metabolism , Adolescent , Adult , Child , Escherichia coli/metabolism , Humans , Middle Aged , Peptide Fragments/chemistry , Young AdultABSTRACT
Hypertrophic scar (HS) has been considered as a great concern for patients and a challenging problem for clinicians as it can cause functional debility, cosmetic disfigurement and psychological trauma. Although many methods have been developed to prevent and treat HS, the scarless healing is still a worldwide medical problem. In this study, palmatine-loaded poly(ε-caprolactone)/gelatin nanofibrous scaffolds (PCL/GE/PALs) were fabricated by electrospinning, and their effects on wound healing and HS formation were investigated. These nanofiber mats exhibit good antibacterial and antioxidant activities. In vitro studies indicate PCL/GE/PAL scaffolds can facilitate the adhesion, spreading and proliferation of L929 fibroblasts. In vivo tests demonstrate the full-thickness wounds treated with PCL/GE/PAL scaffolds heal about 3.5 days earlier than those in the control group. Scar elevation index measurements and histological analyses reveal PCL/GE/PAL scaffolds significantly inhibit HS formation, with the decrease in the thickness of dermis and epidermis, the number of fibroblasts, as well as the density of collagen and microvascular. Accelerating wound healing and inhibiting HS formation of these scaffolds are contributed to the sustained release of palmatine. The present work validates the potential use of palmatine-loaded electrospun nanofibrous scaffold PCL/GE/PALs as a functional wound dressing for healing wounds and preventing HS formation.
Subject(s)
Berberine Alkaloids/chemistry , Caproates/chemistry , Cicatrix, Hypertrophic/pathology , Gelatin/chemistry , Lactones/chemistry , Nanofibers/chemistry , Animals , Anti-Bacterial Agents/pharmacology , Antioxidants/chemistry , Antioxidants/metabolism , Bandages , Cell Line , Cell Proliferation , Collagen/chemistry , Escherichia coli , Female , Fibroblasts/drug effects , Mice , Microbial Sensitivity Tests , Rabbits , Skin/drug effects , Staphylococcus aureus , Tensile Strength , Tissue Engineering , Tissue Scaffolds , Wound HealingABSTRACT
Silver sillago (Sillago sihama) is a commercially important marine fish species in East Asia. In this study, we compared the transcriptome response to hypoxia stress in the gill tissue of S. sihama. The fish were divided into four groups, such as 1 h of hypoxia (hypoxia1h, DO = 1.5 ± 0.1 mg/L), 4 h of hypoxia (hypoxia4h, DO = 1.5 ± 0.1 mg/L), 4 h of reoxygen (reoxygen4h, DO = 8.0 ± 0.2 mg/L) after 4 h of hypoxia (DO = 1.5 mg/L), and normoxia or control (DO = 8.0 ± 0.2 mg/L) groups. Compared to the normoxia group, a total of 3550 genes were identified as differentially expressed genes (DEGs) (log2foldchange > 1 and padj < 0.05), including 1103, 1451 and 996 genes in hypoxia1h, hypoxia4h and reoxygen4h groups, respectively. Only 247 DEGs were differentially co-expressed in all treatment groups. According to Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, DEGs were significantly enriched in steroid biosynthesis, biosynthesis of amino acids, glutathione metabolism and metabolism of xenobiotics by cytochrome P450, ferroptosis and drug metabolism-cytochrome P450 pathways. Of these, the cytochrome P450 (CYP) and glutathione S-transferase (GST) gene families were widely expressed. Our study represents the insights into the underlying molecular mechanisms of hypoxia stress.
ABSTRACT
Scatophagus argus is a new emerging aquaculture fish in East and Southeast Asia. To date, research on reproductive development and regulation in S. argus is lacking. Additionally, genetic and genomic information about reproduction, such as gonadal transcriptome data, is also lacking. Herein, we report the first gonadal transcriptomes of S. argus and identify genes potentially involved in reproduction and gonadal development. A total of 136,561 unigenes were obtained by sequencing of testes (n = 3) and ovaries (n = 3) at stage III. Genes upregulated in males and females known to be involved in gonadal development and gametogenesis were identified, including male-biased dmrt1, amh, gsdf, wt1a, sox9b, and nanos2, and female-biased foxl2, gdf9, bmp15, sox3, zar1, and figla. Serum estradiol-17ß and 11-ketotestosterone levels were biased in female and male fish, respectively. Sexual dimorphism of serum steroid hormone levels were interpreted after expression analysis of 20 steroidogenesis-related genes, including cyp19a1a and cyp11b2. This gonadal transcript dataset will help investigate functional genes related to reproduction in S. argus.
Subject(s)
Fishes/genetics , Gonads/physiology , Sex Characteristics , Transcriptome , Animals , Female , Gonadal Steroid Hormones/blood , Male , RNA-SeqABSTRACT
This study aims to investigate the effect and mechanism of type 2 voltage-gated chloride channel (ClC-2) on myelin development of newborn rats' cerebral white matter with gestational diabetes mellitus (GDM). In this study, GDM model was induced in late pregnant rat model. The alteration of ClC-2 expression in various developmental stages of cerebral white matter with/without being exposed to high glucose was analyzed using RT-PCR, active oxygen detection, TUNEL staining, Western Blot as well as immuno-histochemical staining. Our results showed that ClC-2 mRNA and protein expressions in GDM group were significantly increased in white matter of fetal rats after E18 stage, and elevated the level of TNF-α and iNOS in white matter at P0 and P3 stage of newborn rats. Meanwhile, In GDM group, reactive oxygen species (ROS) levels of the white matter at E18, P0, and P3 stage were significantly higher than control group. Furthermore, the expression level of myelin transcription factor Olig2 at P0 stage and CNPase at P3 stage were strikingly lower than that of the control group. In GDM group, ClC-2 expression in the corpus callosum (CC) and cingulate gyrus (CG) regains, and TUNEL positive cell number were increased at P0 and P3 stage. However, PDGFα positive cell number at P0 stage and CNPase expression at P3 stage were significantly decreased. Caspase-3 was also increased in those white matter regions in GDM group, but p-Akt expression was inhibited. While DIDS (a chloride channel blocker) can reverse these changes. In conclusion, ClC-2 and caspase-3 were induced by GDM, which resulted in apoptosis and myelination inhibition. The effect was caused by repressing PI3K-Akt signaling pathway. Application of ClC-2 inhibitor DIDS showed protective effects on cerebral white matter damage stimulated by high glucose concentration.