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Integrin subunit beta-like 1 (ITGBL1), a member of the epidermal growth factor (EGF)-like protein family, encodes a beta integrin-related protein that is mainly associated with the development of specific tumours and immune-related signalling pathways. This work aimed to explore the possibility that ITGBL1 functions as a novel target gene for immunotherapy and could be a cancer prognostic molecule. The mRNA data for ITGBL1 were obtained from the public databases The Cancer Genome Atlas (TCGA), Genotype-Tissue Expression (GTEx) and Gene Expression Omnibus (GEO). Using GEPIA, the differential expression of ITGBL1 in different tumour stages was identified. Cancer prognostic correlations were explored using Kaplan–Meier survival analysis and forest plots. A combination of Gene Set Enrichment Analysis (GSEA), TIMER2.0 and the R package was applied to analyse the ITGBL1-enriched related pathways. The NCI-60 drug database was examined using CellMinerTM. Cytological experiments were conducted to confirm ITGBL1's impact on cancer cells. Our research has shown that ITGBL1 is differentially expressed in 26 cancers, and high ITGBL1 expression predicts a poorer survival prognosis in some specific cancers. Additionally, we found that ITGBL1 is enriched in immune-related pathways, which are closely linked to immunomodulatory molecules, immune-infiltrating cells, and immunomodulatory factors. The results of tumor mutational burden (TMB) and microsatellite instability (MSI) also indicate that the expression of ITGBL1 is beneficial for improving tumor immunotherapy efficacy. Furthermore, a number of antitumor agents associated with ITGBL1 expression have been identified. Finally, knockdown of ITGBL1 restricts the ability of gastric and colorectal cancer cells to proliferate and migrate. Our study demonstrates that ITGBL1 can be utilized to accurately prognosticate cancer and has opened up new avenues for the investigation of tumor immune mechanisms and the development of more efficacious immunotherapies. [ABSTRACT FROM AUTHOR]

Background: The FXYD family of ion transport regulators have emerged as important modulators of cancer progression and metastasis. However, their expression and roles in ovarian cancer (OCa) have not been systematically investigated. Methods: The expression of FXYD genes in OCa was analyzed using data from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO), as well as independent clinical samples. The prognostic values of FXYD genes were evaluated by Kaplan–Meier and Cox regression analysis. To explore potential mechanisms, bioinformatics approaches including Gene Ontology, KEGG pathway analysis, GSEA and drug sensitivity correlation analysis were performed. OCa cell lines overexpressing FXYD1, FXYD5 or FXYD7 were also generated and their impacts on proliferation, migration and invasion were assessed. Results: FXYD1 and FXYD6 were significantly downregulated while FXYD3, FXYD4 and FXYD5 were upregulated in OCa tissues compared to normal tissues. FXYD1, FXYD5 and FXYD7 were independent adverse prognostic factors for OCa patients. Pathway and drug correlation analysis revealed that FXYD1, FXYD5 and FXYD7 genes regulated diverse oncogenic signaling cascades and modulated the response to various chemotherapeutic agents. Overexpression of FXYD1, FXYD5 or FXYD7 enhanced OCa cell motility and invasiveness in vitro. Conclusion: Our results demonstrate aberrant expression patterns, prognostic values, and oncogenic activities of FXYD genes in OCa. FXYD1, FXYD5 and FXYD7 may serve as biomarkers and therapeutic targets for this disease. Targeting FXYD-mediated signaling represents a promising therapeutic strategy against OCa. [ABSTRACT FROM AUTHOR]

Background: Ovarian development is an important prerequisite and basis for animal reproduction. In many vertebrates, it is regulated by multiple genes and influenced by sex steroid hormones and environmental factors. However, relative information is limited in shellfish. To explore the biological functions and molecular mechanisms of mRNA and non-coding RNA that regulate ovarian development in Scapharca broughtonii, we performed whole transcriptome sequencing analysis on ovaries at three developmental stages. Furthermore, the biological processes involved in the differential expression of mRNA and ncRNA were analyzed. Results: A total of 11,342 mRNAs, 6897 lncRNAs, 135 circRNAs, and 275 miRNAs were differentially expressed. By mapping the differentially expressed RNAs from the three developmental stages of Venn diagram, multiple groups of shared mRNAs and lncRNAs were found to be associated with ovarian development, with some mRNA and ncRNA functions associated with steroid hormone. In addition, we constructed and visualized the lncRNA/circRNA-miRNA-mRNA network based on ceRNA targeting relationships. Conclusions: These findings may facilitate our further understanding the mRNA and ncRNAs roles in the regulation of shellfish reproduction. [ABSTRACT FROM AUTHOR]

Aminotransferases are enzymes found in living organisms that catalyze transfer reactions between amino acids and keto acids, crucial for amino acid metabolism and synthesis. Aminotransferase classes I and II play a vital role in regulating osmolarity, protecting cells, and improving metabolic homeostasis and cellular fitness. To investigate the characteristics of the aminotransferase class I and II gene family and their roles in osmotic pressure regulation in the Jinjiang oyster (Crassostrea ariakensis), the gene structure, chromosomal localization, and phylogeny were characterized and the genes' expression in the gill under high-salt stress was analyzed. In this study, eighteen Aminotransferase class I and II genes, including SPTLCa and SPTLCb, SPTa and SPTb, ALAT2a and ALAT2b, KAT3a and KAT3b, and ASTa, ASTb and ASTc, were identified. The physicochemical properties of 11 family members were stable, with their instability factors less than 40. Subcellular localization prediction showed that aminotransferase classes I and II were localized in the cytoplasm or mitochondria. Chromosomal localization results showed that the 18 aminotransferase class I and II genes were located on eight chromosomes. All members of this gene family had the Aminotran_1_2 structural domain which is associated with osmotic pressure regulation by adjusting the conversion reaction between amino acids and keto acids. Most gene expressions showed an initial increase followed by a decrease from 0 h to 12 h when the oysters were challenged by acute stress using artificial seawater with a salinity of 40. However, the expression of CarAGT2 and CarKAT3b genes showed an increased trend with increasing stress time. This study systematically investigated the bioinformatics characteristics of the aminotransferase class I and II gene family in C. ariakensis and their role in osmotic pressure regulation, which provides scientific data for understanding the potential functions of these genes in physiological adaptation, thereby expanding the research on osmoregulation in bivalves. [ABSTRACT FROM AUTHOR]

The protein kinesin family member 26B (KIF26B) is aberrantly expressed in various cancers. However, its particular role and association with tumor immune infiltration in colon adenocarcinoma (COAD) remain unclear. All original data were downloaded directly from The Cancer Genome Atlas (TCGA), UCSC Xena, and Gene Expression Omnibus (GEO) databases and processed with R 3.6.3. KIF26B expression was analyzed using Oncomine, TIMER, TCGA, GEO databases, and our clinical specimens. KIF26B expression at the protein level was explored with Human Protein Atlas (HPA) database. The upstream miRNAs and lncRNAs were predicted by StarBase and validated using RT-qPCR. Correlation of KIF26B expression with the expression of immune-related or immune checkpoint genes and GSEA analysis of KIF26B-related genes were investigated via R software. Relationship of KIF26B expression with immune biomarkers or tumor immune infiltration levels was studied through GEPIA2 and TIMER databases. KIF26B was upregulated, and its overexpression was closely related to overall survival (OS), disease-specific survival (DSS), progression-free interval (PFI), T stage, N stage, and CEA levels in COAD. MIR4435-2HG/hsa-miR−500a−3p/KIF26B axis was identified as the promising regulatory pathway of KIF26B. KIF26B expression was positively correlated with immune-related genes, tumor immune infiltration, and biomarker genes of immune cells in COAD, and KIF26B-related genes were significantly enriched in macrophage activation-related pathways. Expression of immune checkpoint genes, including PDCD1, CD274, and CTLA4, was also closely related to KIF26B expression. Our results clarified that ncRNA-based increased KIF26B expression was associated with a worse prognosis and high tumor immune infiltration in COAD. [ABSTRACT FROM AUTHOR]

Background : A large proportion of pulmonary embolism (PE) heritability remains unexplained, particularly among the East Asian (EAS) population. Our study aims to expand the genetic architecture of PE and reveal more genetic determinants in Han Chinese. Methods: We conducted the first genome-wide association study (GWAS) of PE in Han Chinese, then performed the GWAS meta-analysis based on the discovery and replication stages. To validate the effect of the risk allele, qPCR and Western blotting experiments were used to investigate possible changes in gene expression. Mendelian randomization (MR) analysis was employed to implicate pathogenic mechanisms, and a polygenic risk score (PRS) for PE risk prediction was generated. Results: After meta-analysis of the discovery dataset (622 cases, 8853 controls) and replication dataset (646 cases, 8810 controls), GWAS identified 3 independent loci associated with PE, including the reported loci FGG rs2066865 (p-value = 3.81 × 10−14), ABO rs582094 (p-value = 1.16 × 10−10) and newly reported locus FABP2 rs1799883 (p-value = 7.59 × 10−17). Previously reported 10 variants were successfully replicated in our cohort. Functional experiments confirmed that FABP2-A163G(rs1799883) promoted the transcription and protein expression of FABP2. Meanwhile, MR analysis revealed that high LDL-C and TC levels were associated with an increased risk of PE. Individuals with the top 10% of PRS had over a fivefold increased risk for PE compared to the general population. Conclusions: We identified FABP2, related to the transport of long-chain fatty acids, contributing to the risk of PE and provided more evidence for the essential role of metabolic pathways in PE development. [ABSTRACT FROM AUTHOR]

Simple Summary: Salinity can affect the physiological, reproductive, and developmental characteristics of marine molluscs. The Chinese razor clam (Sinonovacula constricta) is a marine bivalve that inhabits estuarine and intertidal habitats where salinity is usually lower when compared to open sea waters. The species is also an economically important subject of aquaculture in China. Here, RNA sequencing was used to study the internal mechanism of salt stress response in the Chinese razor clam. Differentially expressed RNAs were identified and lncRNA/circRNA-miRNA-mRNA regulatory networks were successfully constructed. Furthermore, the expression of four candidate genes in the Chinese razor clam subjected to different salinity stress were examined by qRT-PCR. The results of this study will improve our understanding of genetic-level responses to salinity changes in the Chinese razor clam. Moreover, the acquired information may be useful for optimization of the artificial breeding of the species under aquaculture conditions. The Chinese razor clam (Sinonovacula constricta) is an important for Chinese aquaculture marine bivalve that naturally occurs across intertidal and estuarine areas subjected to significant changes in salinity level. However, the information on the molecular mechanisms related to high salinity stress in the species remain limited. In this study, nine gill samples of S. constricta treated with 20, 30, and 40 ppt salinity for 24 h were used for whole-transcriptome RNA sequencing, and a regulatory network of competing endogenous RNAs (ceRNAs) was constructed to better understand the mechanisms responsible for adaptation of the species to high salinity. A total of 83,262 lncRNAs, 52,422 mRNAs, 2890 circRNAs, and 498 miRNAs were identified, and 4175 of them displayed differential expression pattern among the three groups examined. The KEGG analyses of differentially expressed RNAs evidenced that amino acid synthesis and membrane transport were the dominant factors involved in the adaptation of the Chinese razor clam to acute salinity increase, while lipid metabolism and signaling played only a supporting role. In addition, lncRNA/circRNA-miRNA-mRNA regulatory networks (ceRNA network) showed clearly regulatory relationships among different RNAs. Moreover, the expression of four candidate genes, including tyrosine aminotransferase (TAT), hyaluronidase 4 (HYAL4), cysteine sulfinic acid decarboxylase (CSAD), and ∆1-pyrroline-5-carboxylate synthase (P5CS) at different challenge time were detected by qRT-PCR. The expression trend of TAT and HYAL4 was consistent with that of the ceRNA network, supporting the reliability of established network. The expression of TAT, CSAD, and P5CS were upregulated in response to increased salinity. This might be associated with increased amino acid synthesis rate, which seems to play an essential role in adaptation of the species to high salinity stress. In contrast, the expression level of HYAL4 gene decreased in response to elevated salinity level, which is associated with reduction Hyaluronan hydrolysis to help maintain water in the cell. Our findings provide a very rich reference for understanding the important role of ncRNAs in the salinity adaptation of shellfish. Moreover, the acquired information may be useful for optimization of the artificial breeding of the Chinese razor clam under aquaculture conditions. [ABSTRACT FROM AUTHOR]

Simple Summary: Paramyosin is an important myofibrillar protein in smooth muscle in molluscs that is not present in vertebrate muscles. This study characterized its sequence feature and expression patterns in Yesso scallop Patinopecten yessoensis and revealed the unique phosphorylation sites in scallops. The mRNA and protein expression of paramyosin was mainly found in foot and smooth adductor muscle. At late larval stages, strong paramyosin mRNA signals were detected in the symmetric positions of anterior and posterior adductor muscles. The present findings support that paramyosin may serve as the most important component of smooth muscle assembly during muscle development and catch regulation in scallops. Paramyosin is an important myofibrillar protein in molluscan smooth muscle. The full-length cDNA encoding paramyosin has been identified from Yesso scallop Patinopecten yessoensis. The length of paramyosin molecule has been found to be 3715 bp, which contains an open reading frame (ORF) of 2805 bp for 934 amino acid residues. Characterization of P. yessoensis paramyosin reveals the typical structural feature of coiled-coil protein, including six α-helix (α1-α6) and one coil (η) structures. Multiple phosphorylation sites have been predicted at the N-terminus of paramyosin, representing the unique phosphorylation sites in scallops. The highest levels of mRNA and protein expression of paramyosin have been found in foot and the smooth adductor muscle. According to whole-mount in situ hybridization (WISH), strong paramyosin mRNA signals were detected in the symmetric positions of anterior and posterior adductor muscles at late larval stages. These findings support that paramyosin may serve as the most important components for myogenesis and catch regulation in scallops. The present findings will not only help uncover the potential function of myofibrillar proteins in molluscs but also provide molecular evidence to infer evolutionary relationships among invertebrates. [ABSTRACT FROM AUTHOR]

Long noncoding RNA (lncRNA) is a crucial factor in the progression of insulin resistance (IR). Resveratrol (RSV) exhibits promising therapeutic potential for IR. However, there are few studies on whether RSV improves IR through lncRNA. This study aimed to determine whether RSV could influence the expression of lncRNA and to elucidate the underlying mechanism. Mice were divided into three groups: control group, high-fat diet (HFD) group, and HFD + RSV group. We conducted a high-throughput sequencing analysis to detect lncRNA and mRNA expression signatures and the ceRNA-network in the skeletal muscles of mice that were fed an HFD to induce IR. Hierarchical clustering, gene enrichment, and gene ceRNA-network analyses were subsequently conducted. Differentially expressed lncRNAs were selected and validated via reverse transcription-quantitative polymerase chain reaction (RT-qPCR). The biological functions of the selected lncRNAs were investigated by silencing the target genes via lentivirus transfection of C2C12 mouse myotube cells. RSV treatment reversed the expression of 338 mRNAs and 629 lncRNAs in the skeletal muscles of mice with HFD-induced IR. The results of the Gene Ontology and Kyoto Encyclopedia of Genes and Genomes database analyses indicated that the differentially expressed mRNAs modulated type II diabetes mellitus. After validating randomly selected lncRNAs via RT-qPCR, we identified a novel lncRNA, NONMMUT044897.2, which was upregulated in the HFD group and reversed with RSV treatment. Additionally, NONMMUT044897.2 was proven to function as a ceRNA of microRNA- (miR-) 7051-5p. Suppressor of Cytokine Signaling 1 (SOCS1) was confirmed as a target of miR-7051-5p. We further performed lentivirus transfection to knock down NONMMUT044897.2 in vitro and found that NONMMUT044897.2 silenced SOCS1 and potentiated the insulin signaling pathway. Hence, RSV mimicked the silencing effect of lentivirus transfection on NONMMUT044897.2. Our study revealed that RSV reduced IR in mouse skeletal muscles via the regulation of NONMMUT044897.2. [ABSTRACT FROM AUTHOR]

Background. The acidic characteristics of the tumor microenvironment (TME) are attributed to cancer cells' needs of metabolism which produce a large amount of H+. In order not to affect its own life activities, it needs to release H+ into the intercellular space through an efficient Na+/H+ exchanger. On account of the intestine whose physiological function is highly dependent on intestinal pH value, NHE family members may play a critical role in the occurrence and development of colorectal cancer (CRC). Methods. TCGA, GEPIA2, ONCOMINE, UALCAN, STRING, TIMER, Cytoscape, TargetScan, ENCORI, LncBase v.2, DNMIVD, HPA, and CellMinerTM databases were used in our study. Results. The mRNA expressions of SLC9A1, SLC9A2, SLC9A3, and SLC9A9 were evidently lower in COAD than in normal samples; however, the mRNA expressions of SLC9A5, SLC9A8, and SLC9B2 were higher. Besides, mRNA expressions of NHE family were extremely associated with clinicopathological features, tumor immune microenvironment and stemness score, DNA methylation, and patient prognosis in COAD. Moreover, we conjectured that NHE family may play a role through MAPK or ErbB signaling pathway according to the results of GO/KEGG enrichment analysis. At last, we found that NHE family members were key factors of various kinds of cancers. Conclusion. Our study indicated that NHE family represented new diagnostic and therapeutic targets for CRC, which could have important significance for the clinical treatment of CRC. [ABSTRACT FROM AUTHOR]

Specifically, The image for Figure 5C, NC, has overlap with the image for Figure 6D, NC. This retraction relates to this paper Sun F, Wu K, Yao Z, et al. I Onco Targets Ther i . 2020;13:6755-6765. [Extracted from the article]

Ribosomal protein S15A (RPS15A), a member of the ribosomal protein gene family, was demonstrated to be closely associated with tumorigenesis in multiple human malignancies. Nevertheless, the role of RPS15A in the progression of renal cell carcinoma (RCC) remains unknown. In the present study, by comparing the publicly available data from RCC tissues and reverse transcription-quantitative polymerase chain reaction results, it was identified that RPS15A was upregulated in RCC tissues and cell lines (P<0.001). Notably, knockdown of RPS15A suppressed 786-O cell proliferation (P<0.001) and promoted its apoptosis/necrotic (P=0.0001) in vitro. Additionally, tumour formation and growth of transfected 786-O cells were observed to be restrained in a mouse model (P<0.05). Subsequent to analysing the microarray data, 747 genes were differentially expressed in the RPS15A-knockdown 786-O cells. The enriched canonical pathways, diseases and functions of differentially expressed genes, and the interactive network of RPS15A in RCC were successfully constructed by ingenuity pathway analysis. Overall, the present results provided a preliminary experimental basis for RPS15A as a novel oncogene and potential therapeutic target in RCC. [ABSTRACT FROM AUTHOR]

Endometrial polyps (EPs) are localized benign overgrowths at the endometrium, with currently unknown aetiology and pathogenesis. Although symptoms of EP can be alleviated or resolved by hysteroscopic polypectomy, a significant fraction of individuals develop recurrent EPs after initial EP removal. In rare cases, EPs may also undergo malignant transformation. In-depth understanding of the mechanisms that are involved in EP development is urgently needed. Recent works indicate that dysregulations in the immune system participate in the development of a variety of symptoms, such as aging, obesity and hypertension, many of which are EP risk factors. Based on these discoveries, we investigated the cellular immune system in premenopausal women with and without EP. Compared to EP-free controls, the women with EP presented significantly higher RORC expression but unchanged TBX21 and FOXP3 expression in the circulating CD4+ T cells. When stimulated with PMA/ionomycin, CD4+ T cells from women with EP presented significantly higher interferon (IFN)-γ and interleukin (IL)-17 secretion, and lower transforming growth factor (TGF)-β secretion. Hysteroscopic polypectomy did not significantly alter the composition of CD4+ T cells, as the women with EP presented a similar upregulation of Th17 inflammation and a downregulation of regulatory T cell (Treg) response postoperatively. Notably, in women that developed recurrent EP, the CD4+ T cells presented higher preoperative and postoperative RORC, IFN-γ, and IL-17 expression, as well as lower postoperative FOXP3 and TGF-β expression, than hysteroscopic polypectomy-treated women without EP recurrence. These data demonstrated an association between CD4+ T cell imbalance and recurrent EP development. [ABSTRACT FROM AUTHOR]

Pneumonia is a common respiratory disease worldwide, which is preventable and treatable; however, it is recognized as a leading cause of mortality in children. The present study aimed to investigate the role and mechanism of microRNA (miR)-20a in inflammation in pediatric pneumonia. Clinical serum samples were collected from children with pneumonia and healthy children. Initially, the serum expression levels of miR-20a were detected by reverse transcription-quantitative polymerase chain reaction. Subsequently, A549 cells were randomly divided into four groups: Control group; lipopolysaccharide (LPS; 1 μg/ml) group; LPS + miR-20a group; and LPS + miR-20a + pyrrolidine dithiocarbamate (PDTC; 100 mmol/l) group. The concentrations of interleukin-6 (IL-6), tumor necrosis factor (TNF)-α and C-reactive protein (CRP) in clinical serum samples and A549 cells were determined by ELISA. In addition, the protein expression levels of inhibitor of nuclear factor (NF)-κB α (IκBα) and phosphorylated (p)-NF-κB were measured by western blotting. The results demonstrated that miR-20a was upregulated in children with pneumonia and in lung cells with LPS-induced inflammatory injury (P<0.01). In addition, compared with the LPS group, cells in the LPS + miR-20a group exhibited increased expression levels of IL-6, TNF-α and CRP (P<0.05). Overexpression of miR-20a also resulted in upregulation of the expression levels of IκBα and p-NF-κB compared with in the LPS group (P<0.05). Furthermore, treatment with the NF-κB inhibitor PDTC inhibited the expression of inflammatory factors compared with in the LPS + miR-20a group (P<0.05). In conclusion, the present study indicated that miR-20a is upregulated in pediatric pneumonia, and overexpression of miR-20a may promote inflammation through activation of the NF-κB signaling pathway. [ABSTRACT FROM AUTHOR]

The Yesso scallop Patinopecten yessoensis displays polymorphism in shell colors, which is of great interest for the scallop industry. To identify genes involved in the shell coloration, in the present study, we investigate the transcriptome differences by Illumina digital gene expression (DGE) analysis in two extreme color phenotypes, Red and White. Illumina sequencing yields a total of 62,715,364 clean sequence reads, and more than 85% reads are mapped into our previously sequenced transcriptome. There are 25 significantly differentially expressed genes between Red and White scallops. EPR (Electron paramagnetic resonance) analysis has identified EPR spectra of pheomelanin and eumelanin in the red shells, but not in the white shells. Compared to the Red scallops, the White scallops have relatively higher mRNA expression in tyrosinase genes, but lower expression in other melanogensis-associated genes. Meantime, the relatively lower tyrosinase protein and decreased tyrosinase activity in White scallops are suggested to be associated with the lack of melanin in the white shells. Our findings highlight the functional roles of melanogensis-associated genes in the melanization process of scallop shells, and shed new lights on the transcriptional and post-transcriptional mechanisms in the regulation of tyrosinase activity during the process of melanin synthesis. The present results will assist our molecular understanding of melanin synthesis underlying shell color polymorphism in scallops, as well as other bivalves, and also help the color-based breeding in shellfish aquaculture. [ABSTRACT FROM AUTHOR]

Ferritin, the principle cytosolic iron storage protein in the majority of living organisms, has important roles during immune process in invertebrates. Detailed information about ferritin in the ark shell Scapharca broughtonii , however, has been very limited. In this study, full-length ferritin (termed SbFer ) was cloned by the rapid amplication of cDNA ends (RACE) method based upon the sequence from the transcriptome library. The cDNA contained a 182 bp 5′-untranslated region, a 519 bp open reading frame encoding a polypeptide of 172 amino acids, a 229 bp 3′-untranslated region, and three introns (902, 373 and 402 bp) embedded in four exons. There was an iron response element (IRE) in the 5′-untranslated region. The deduced amino acid sequence of SbFer possessed many characteristics of vertebrate H type ferritin, shared 63%–91% identity with mollusks and greater identity with vertebrate H type ferritin compared to the L type. The SbFer gene expression pattern examined by quantitative real-time PCR showed ferritin mRNA was expressed in all ark shell tissues examined. The highest levels of expression were found in hemocytes with decreasing levels of expression in foot, mantle, gill, adductor muscle and hepatopancreas. A challenge with Vibrio anguillarum resulted in time-dependent significant upregulation of SbFer mRNA, indicating SbFer participated actively in the bacterial defense process. Further analysis of the antibacterial activity indicated recombinant SbFer could function as an immune antibacterial agent to both Gram-positive and Gram-negative bacteria. Taken together, these results suggested strongly that ferritin of the ark shell is involved in immune defense against microbial infection and it is a constitutive and inducible acute-phase protein. [ABSTRACT FROM AUTHOR]

The number of B cells is increased and the O-glycans of IgA1 are incompletely galactosylated in IgA nephropathy (IgAN). Here we report that expression of phosphatase and tensin homolog (PTEN) and Cosmc is decreased in B cells, and correlates with B cell number and the aberrant glycosylation of IgA1 in IgAN. Patients with IgAN exhibit higher miR-374b in B cells compared to controls. We show that miR-374b targets PTEN and Cosmc by luciferase assays and western blot analysis. Inhibition of miR-374b increased PTEN and Cosmc expression, and prevented cell proliferation and aberrant glycosylation of IgA1, thus representing a new therapeutic approach for IgAN. [ABSTRACT FROM AUTHOR]

Sheep is the representative of the artiodactyla and is an agriculturally important animal, but limited knowledge is available with regard to its immunoglobulin genes and their expression mechanisms in the sheep. Based on the recently released sheep genome, we have characterized the genomic organization of the sheep immunoglobulin light gene loci. The sheep Igλ locus, located on chromosome 17, contains 2 C λ segments each preceded by a J λ , but the C λ 2 appears to be a pseudogene. A total of 42 V λ segments (14 potentially functional genes, 1 ORF and 27 pseudogenes) were identified. In contrast, the Igκ locus on chromosome 3 contains only a single C κ gene, 3 J k segments and 13 V κ segments (8 potentially functional genes and 5 pseudogenes). Analysis of junctions of the recombined VJ transcripts revealed a restricted V λ 4–J λ 1– C λ 1 recombination and V k 6–J k 3–C κ recombination, respectively encode most of λ and κ chain antibody repertoire in the sheep despite more potential germline encoded combinatorial diversity. Therefore, the sheep may use gene conversion in combination with somatic hypermutation for antibody repertoire formation. [ABSTRACT FROM AUTHOR]

Vitellogenin (Vg), the major precursor of the egg-yolk proteins, has been found to play an immune role in fish and protochordate amphioxus, however, no study on the immune function of Vg in invertebrates has ever been studied before. In this study, the complete cDNA of Vg was identified from the scallop Patinopecten yessoensis (termed PyVg ). The cDNA contained an open reading frame (ORF) of 6888 bp, encoding a polypeptide of 2295 amino acid protein, which had an N-terminal signal peptide followed by the mature Vg. The mature Vg had the domains Vitellogenin_N, domain of unknown function 1943 (DUF1943) and von Willebrand factor type D domain (VWD) as well as the consensus cleavage site (R-X-R/K-R) and conserved motif (KTIGNAG). Tissue distribution assay revealed that PyVg transcripts were predominantly present in the ovary and hepatopancreas, and its expression profile in ovary well reflected the annual cycle of vitellogenesis. Interestingly, bacterial challenge caused a significant change in PyVg expression, hinting an involvement of PyVg in the acute phase response in P. yessoensis . Consistently, recombinant DUF1943 and VWD domains both could interact with LTA and LPS on bacterial wall, and purified native PyVg displayed a broad-spectrum antibacterial activity against both Gram-negative ( Escherichia coli and Vibrio anguillarum ) and Gram-positive bacteria ( Staphylococcus aureus ). Overall, these data indicate that Vg is a pattern recognition molecule with bacterial growth-inhibiting activity in the scallop. [ABSTRACT FROM AUTHOR]

The expression of At4g34880 gene encoding amidase in Arabidopsis was characterized in this study. A promoter region of 1.5 kb on the upstream of the start codon of the gene (referred as AmidP) was fused with uidA (GUS) reporter gene, and transformed into Arabidopsis plant for determining its spatial expression. The results indicated that AmidP drived GUS expression in vascular system, predominately in leaves. Truncation analysis of AmidP demonstrated that VASCULAR VEIN ELEMENT (VVE) motif with a region of 176 bp sequence (−1500 to −1324) was necessary and sufficient to direct the vascular vein specific GUS expression in the transgenic plant. Tandem copy of VVE increased vascular system expression, and 5′- and 3′- deletions of VVE motif in combination with a truncated −65 CaMV 35S minimal promoter showed that 11bp cis-acting element, naming DOF2 domain, played an essential role for the vascular vein specific expression. Meanwhile, it was also observed that the other cis-acting elements among the VVE region are also associated with specificity or strength of GUS activities in vascular system. [ABSTRACT FROM AUTHOR]

Regulator of Cullins-1 (ROC1) is a key subunit in the Cullin-RING ligase (CRL) protein complex. Overexpression of ROC1 protein is associated with tumor progression and poor prognosis of non-muscle invasive bladder transitional cell carcinoma (NMIBC). This study was designed to assess the effects of ROC1 knockdown in bladder cancer cells and to determine the potential mechanisms involved. A total of 112 bladder cancer tissue specimens were recruited for immunohistochemical analyses of ROC1 overexpression. Bladder cancer cell lines were used to knockdown ROC1 expression using ROC1 siRNA. Our data showed that ROC1 knockdown remarkably inhibited bladder cancer cell growth, arrested cells at the G2 phase of the cell cycle, and induced the p53-dependent cell senescence. Molecularly, G2 arrest was associated with upregulation of p21, p27, cyclin B1, and Cdc2 proteins. ROC1 knockdown induced-senescence functioned through p53/p21 pathway. Knockdown of p21 expression partially rescued ROC1 knockdown-induced growth inhibition in cancer cells. Furthermore, nude mouse xenograft analyses confirmed these in vitro data. In conclusion, data from the current study indicate that ROC1 plays an essential role in bladder cancer progression and could serve as a novel anticancer target for bladder transitional cell carcinoma (BTCC). [ABSTRACT FROM AUTHOR]

Long noncoding RNAs have been shown to have important regulatory roles in cancer biology, and long noncoding RNA 19 (H19) is essential for human tumor growth. However, little is known about how abnormal expression of H19 contributes to bladder cancer cell proliferation. In this study, we first evaluated the expression of H19 in bladder cancer tissues by real-time PCR, and defined the biological functions. We found that H19 expression levels were remarkably increased in bladder cancer tissues as compared with adjacent normal control tissue, and forced expression of H19 promoted bladder cancer cell proliferation in vitro. Inhibitor of DNA binding/differentiation 2 ( ID2) expression levels were upregulated in bladder cancer tissues and in bladder cancer cells. A significant positive correlation was observed between H19 levels and ID2 levels in vivo. We further demonstrated that overexpression of H19 resulted in a significant increase in the expression of ID2, whereas H19 knockdown decreased ID2 expression in vitro. Gain-of-function and loss-of-function studies demonstrated that upregulated H19 increased bladder cancer cell proliferation by increasing ID2 expression. In conclusion, upregulated H19 increases bladder cancer growth by regulating ID2 expression, and thus may be helpful in the development of effective treatment strategies for bladder cancer. Structured digital abstract TfR1-Cp and TfR1-Cp bind by comigration in gel electrophoresis (View interaction), HSA and TfR1-Cp bind by comigration in gel electrophoresis (View interaction), SPPL2B and TfR1-NTF colocalize by fluorescence microscopy (View interaction), SPPL2A and TfR1-NTF colocalize by fluorescence microscopy (View interaction), HSA binds to TfR1-Cp by pull down (View interaction), TfR1-Cp and TfR1-Cp bind by comigration in gel electrophoresis (View interaction) [ABSTRACT FROM AUTHOR]

Abstract Hemoglobin, the main component of haemolymph, is widely distributed in animals. Although its important oxygen transport functions has been extensively reported, studies on the immune function of hemoglobin in mollusc are few. Research on immune of hemoglobin of ark shell Scapharca broughtonii attracted more and more attention due to its ownership of erythrocyte comparing with many other shellfish. In this study, the hemoglobin cDNA of S. broughtonii was cloned by EST and RACE methods (named as SbHb ). Sequence analysis revealed that the cDNA was 946 bp in length, including an open reading frame (ORF) of 459 bp which encoded a polypeptide of 152 amino acid residues, and a 5′-untranslated region (UTR) of 313 bp, a 3′-UTR of 174 bp. Sequence and homology analysis showed that the SbHb shared similarity with that of other related species. The mRNA expression profiles of SbHb in tested tissues analyzed by quantitative real-time PCR (qRT-PCR) revealed that the mRNA of SbHb could be all detected in foot, gill, mantle, adductor muscle, haemocytes and hepatopancreas, and the highest level was found in the haemocytes, which is 163.2 times higher than that in adductor muscle. Vibrio anguillarum stimulation and hypoxia treatment both had significant impact on the expression of SbHb , which showed the same trends as increasing first to the highest at 16 h after treatment and then followed by declining. Recombinant protein of SbHb (rSbHb) was successfully obtained by prokaryotic expression, and further function analysis indicated obviously that the rSbHb had very strong phenoloxidase-like activity (PO-like activity) and it could remarkably inhibit growth of gram-negative bacteria V. anguillarum. All the data suggested that the SbHb plays a significant role in the process of antibacterial and anoxia tolerance reaction in S. broughtonii, providing the evidence that SbHb is a key immune factor. Highlights • Full length cDNA of hemoglobin in S. broughtonii ( SbHb ) and recombinant protein SbHb are obtained. • Biochemical analysis indcates that SbHb is involved in the acute phase response. [ABSTRACT FROM AUTHOR]

Manganese superoxide dismutase (MnSOD) is one of the key members of the antioxidant defense enzyme family, however, data regarding to the immune function of MnSOD in mollusks still remain limited now. In this study, a full-length MnSOD cDNA was identified by rapid amplification of cDNA ends (RACE) method from cDNA library of ark shell Scapharca broughtonii (termed SbMnSOD ). The cDNA contained an open reading frame (ORF) of 696 bp which encoded a polypeptide of 232 amino acids, a 5′-UTR with length of 32 bp and a 3′-UTR of 275 bp. Four putative amino acid residues (His-57, His-105, Asp-190 and His-194) responsible for manganese coordination were located in the most highly conserved regions of SbMnSOD and the signature sequence (DVWEHAYY) also existed in SbMnSOD . The deduced amino acid sequence of SbMnSOD shared high homology to MnSOD from other species. All those data revealed that the SbMnSOD was a novel member of the MnSOD family. The mRNA expression profiles of SbMnSOD in tissues of foot, gill, mantle, adductor muscle, hemocytes and hepatopancreas analyzed by quantitative real-time PCR (qRT-PCR) suggested the mRNA transcripts of SbMnSOD distributed in all the examined tissues. Importantly, Vibrio anguillarum challenge resulted in the increased expression of SbMnSOD m RNA with a regular change trend in all examined tissues, indicating SbMnSOD actively participated in the immune response process. What's more, further analysis on the antibacterial activity of the recombinant SbMnSOD showed that the fusion protein could remarkably inhibit growth of both Gram-positive and Gram-negative bacteria. The present results clearly suggested that SbMnSOD was an acute phase protein involved in the immune reaction in S. broughtonii . [ABSTRACT FROM AUTHOR]

[Display omitted] • This study used a whole-body exposure dynamic inhalation equipment, which can simulate exposure in actual working environments. • Coal dust exposure can regulate the polarization of rat pulmonary macrophages. • Short-term exposure (inflammatory phase) is characterized by M1 macrophages, accompanied by high expression of chemokines and inflammatory cytokines, while medium to long-term exposure (fibrosis phase) is manifested as by M2 macrophages, accompanied by high expression of anti-inflammatory cytokines. • The CCL5 may play an important role in the pathological progression of coal worker pneumoconiosis and deserves further research. Coal dust is the main occupational hazard factor during coal mining operations. This study aimed to investigate the role of macrophage polarization and its molecular regulatory network in lung inflammation and fibrosis in Sprague-Dawley rats caused by coal dust exposure. Based on the key exposure parameters (exposure route, dose and duration) of the real working environment of coal miners, the dynamic inhalation exposure method was employed, and a control group and three coal dust groups (4, 10 and 25 mg/m3) were set up. Lung function was measured after 30, 60 and 90 days of coal dust exposure. Meanwhile, the serum, lung tissue and bronchoalveolar lavage fluid were collected after anesthesia for downstream experiments (histopathological analysis, RT-qPCR, ELISA, etc.). The results showed that coal dust exposure caused stunted growth, increased lung organ coefficient and decreased lung function in rats. The expression level of the M1 macrophage marker iNOS was significantly upregulated in the early stage of exposure and was accompanied by higher expression of the inflammatory cytokines TNF-α, IL-1β, IL-6 and the chemokines IL-8, CCL2 and CCL5, with the most significant trend of CCL5 mRNA in lung tissues. Expression of the M2 macrophage marker Arg1 was significantly upregulated in the mid to late stages of coal dust exposure and was accompanied by higher expression of the anti-inflammatory cytokines IL-10 and TGF-β. In conclusion, macrophage polarization and its molecular regulatory network (especially CCL5) play an important role in lung inflammation and fibrosis in SD rats exposed to coal dust by dynamic inhalation. [ABSTRACT FROM AUTHOR]

Cancer patients commonly experience high levels of psychological stress, which poses significant risks to their well-being. Radiotherapy is a primary treatment modality for cancer; however, it often leads to intestinal injuries in these patients. Nevertheless, the impact of mental stress on radiotherapy-intertwined complications remains unclear. To induce intestinal injury, we employed total abdominal irradiation in our experimental model. We conducted high-throughput sequencing to analyze the expression profile of miRNAs in the hippocampus. We observed that mice with depression exhibited more severe intestinal injuries following total abdominal irradiation. Remarkably, oral administration of Marasmius androsaceus not only alleviated the depressive phenotype but also mitigated radiation-induced intestinal toxicity. Notably, this radioprotective effect was not observed in mice without depression. Depression disrupted the hippocampal miRNA expression profile in mice subjected to local irradiation of the abdomen, leading to the accumulation of miR-139–5p and miR-184–3p in the hippocampus, serum, and small intestine tissues. However, treatment with Marasmius androsaceus reprogrammed the miRNA expression signature in mice with depression. Furthermore, intravenous injection of antagomirs targeting miR-139–5p and miR-184–3p ameliorated depression, up-regulated Spn expression, reduced radiation enteritis, and improved the integrity of the small intestine in irradiated mice. Our findings demonstrate the efficacy of Marasmius androsaceus , a small mushroom, in alleviating depression-aggravated intestinal toxicity following radiotherapy by reprogramming hippocampal miRNA expression. [Display omitted] • Depression aggravates intestinal radiation injury in mouse models. • Marasmius androsaceus mitigates intestinal toxicity in depression-afflicted mice. • Marasmius androsaceus reprograms the hippocampal miRNA expression. • Marasmius androsaceus mitigates radiation injury in a miRNA-dependent manner. [ABSTRACT FROM AUTHOR]

Abstract: The objective of this study was to estimate the parameters necessary to determine whether the genetic expression of fleece traits in Inner Mongolia Arbas cashmere goats was unified at different ages. Fleece traits, including fiber diameter (FD) and fiber length (FL), were measured between 2008 and 2012, as goats aged from 1 to 5 years old, and were modeled using repeatability and several multivariate models that varied in covariance structure. Bayesian information criteria were used to choose the most ideal model. In the preferred model, FD could be partitioned into yearlings and older goats, while FL could be partitioned into yearlings, 2 year olds, and older goats. The heritabilities of FD in yearlings and older goats were 0.35 and 0.27, respectively, and the genetic correlation between yearlings and older goats was 0.93. For FL, the estimates of heritability were 0.18, 0.38, and 0.29 within the 3 age groups. The genetic correlations were 0.94 for yearlings with 2 year olds and older goats and close to 1.00 for 2 year olds with older goats. These findings provide useful information for designing more ideal and effective breeding programs to improve fiber quality. [Copyright &y& Elsevier]

Abstract: lncRNA H19 is essential for human tumor growth. However, little is known about whether H19 regulates bladder cancer metastasis. Here we found that H19 levels are remarkably increased in bladder cancer tissues, and upregulated H19 promotes bladder cancer cell migration in vitro and in vivo. H19 is associated with enhancer of zeste homolog 2 (EZH2), and that this association results in Wnt/β-catenin activation and subsequent downregulation of E-cadherin. A significant negative correlation is also observed between H19 levels and E-cad levels in vivo. These data suggest that upregulated H19 enhances bladder cancer metastasis by associating with EZH2 and inhibiting E-cad expression. [Copyright &y& Elsevier]