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1.
Proc Natl Acad Sci U S A ; 121(10): e2317026121, 2024 Mar 05.
Article in English | MEDLINE | ID: mdl-38408250

ABSTRACT

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has been detected in almost all organs of coronavirus disease-19 patients, although some organs do not express angiotensin-converting enzyme-2 (ACE2), a known receptor of SARS-CoV-2, implying the presence of alternative receptors and/or co-receptors. Here, we show that the ubiquitously distributed human transferrin receptor (TfR), which binds to diferric transferrin to traffic between membrane and endosome for the iron delivery cycle, can ACE2-independently mediate SARS-CoV-2 infection. Human, not mouse TfR, interacts with Spike protein with a high affinity (KD ~2.95 nM) to mediate SARS-CoV-2 endocytosis. TfR knock-down (TfR-deficiency is lethal) and overexpression inhibit and promote SARS-CoV-2 infection, respectively. Humanized TfR expression enables SARS-CoV-2 infection in baby hamster kidney cells and C57 mice, which are known to be insusceptible to the virus infection. Soluble TfR, Tf, designed peptides blocking TfR-Spike interaction and anti-TfR antibody show significant anti-COVID-19 effects in cell and monkey models. Collectively, this report indicates that TfR is a receptor/co-receptor of SARS-CoV-2 mediating SARS-CoV-2 entry and infectivity by likely using the TfR trafficking pathway.


Subject(s)
COVID-19 , Animals , Humans , Mice , Angiotensin-Converting Enzyme 2/genetics , Angiotensin-Converting Enzyme 2/metabolism , Peptidyl-Dipeptidase A/metabolism , Protein Binding , Receptors, Transferrin/genetics , Receptors, Transferrin/metabolism , SARS-CoV-2/metabolism , Spike Glycoprotein, Coronavirus/metabolism
2.
Nature ; 586(7830): 572-577, 2020 10.
Article in English | MEDLINE | ID: mdl-32726802

ABSTRACT

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes a respiratory disease called coronavirus disease 2019 (COVID-19), the spread of which has led to a pandemic. An effective preventive vaccine against this virus is urgently needed. As an essential step during infection, SARS-CoV-2 uses the receptor-binding domain (RBD) of the spike protein to engage with the receptor angiotensin-converting enzyme 2 (ACE2) on host cells1,2. Here we show that a recombinant vaccine that comprises residues 319-545 of the RBD of the spike protein induces a potent functional antibody response in immunized mice, rabbits and non-human primates (Macaca mulatta) as early as 7 or 14 days after the injection of a single vaccine dose. The sera from the immunized animals blocked the binding of the RBD to ACE2, which is expressed on the cell surface, and neutralized infection with a SARS-CoV-2 pseudovirus and live SARS-CoV-2 in vitro. Notably, vaccination also provided protection in non-human primates to an in vivo challenge with SARS-CoV-2. We found increased levels of RBD-specific antibodies in the sera of patients with COVID-19. We show that several immune pathways and CD4 T lymphocytes are involved in the induction of the vaccine antibody response. Our findings highlight the importance of the RBD domain in the design of SARS-CoV-2 vaccines and provide a rationale for the development of a protective vaccine through the induction of antibodies against the RBD domain.


Subject(s)
Antibodies, Viral/immunology , Betacoronavirus/immunology , Coronavirus Infections/immunology , Coronavirus Infections/prevention & control , Pandemics/prevention & control , Pneumonia, Viral/immunology , Pneumonia, Viral/prevention & control , Spike Glycoprotein, Coronavirus/chemistry , Spike Glycoprotein, Coronavirus/immunology , Viral Vaccines/immunology , Animals , Antibodies, Neutralizing/immunology , COVID-19 , COVID-19 Vaccines , Humans , Macaca mulatta/immunology , Macaca mulatta/virology , Mice , Mice, Inbred BALB C , Mice, Inbred C57BL , Models, Animal , Models, Molecular , Protein Domains , SARS-CoV-2 , Serum/immunology , Spleen/cytology , Spleen/immunology , T-Lymphocytes/immunology , Vaccination
3.
Nature ; 583(7818): 830-833, 2020 07.
Article in English | MEDLINE | ID: mdl-32380511

ABSTRACT

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the cause of coronavirus disease 2019 (COVID-19), which has become a public health emergency of international concern1. Angiotensin-converting enzyme 2 (ACE2) is the cell-entry receptor for severe acute respiratory syndrome coronavirus (SARS-CoV)2. Here we infected transgenic mice that express human ACE2 (hereafter, hACE2 mice) with SARS-CoV-2 and studied the pathogenicity of the virus. We observed weight loss as well as virus replication in the lungs of hACE2 mice infected with SARS-CoV-2. The typical histopathology was interstitial pneumonia with infiltration of considerable numbers of macrophages and lymphocytes into the alveolar interstitium, and the accumulation of macrophages in alveolar cavities. We observed viral antigens in bronchial epithelial cells, macrophages and alveolar epithelia. These phenomena were not found in wild-type mice infected with SARS-CoV-2. Notably, we have confirmed the pathogenicity of SARS-CoV-2 in hACE2 mice. This mouse model of SARS-CoV-2 infection will be valuable for evaluating antiviral therapeutic agents and vaccines, as well as understanding the pathogenesis of COVID-19.


Subject(s)
Betacoronavirus/pathogenicity , Coronavirus Infections/pathology , Coronavirus Infections/virology , Lung/pathology , Peptidyl-Dipeptidase A/genetics , Peptidyl-Dipeptidase A/metabolism , Pneumonia, Viral/pathology , Pneumonia, Viral/virology , Transgenes , Angiotensin-Converting Enzyme 2 , Animals , Antigens, Viral/immunology , Antigens, Viral/metabolism , Betacoronavirus/immunology , Betacoronavirus/metabolism , Bronchi/pathology , Bronchi/virology , COVID-19 , Coronavirus Infections/immunology , Disease Models, Animal , Epithelial Cells/pathology , Epithelial Cells/virology , Female , Humans , Immunoglobulin G/immunology , Lung/immunology , Lung/virology , Lymphocytes/immunology , Macrophages, Alveolar/immunology , Macrophages, Alveolar/virology , Male , Mice , Mice, Transgenic , Pandemics , Pneumonia, Viral/immunology , Receptors, Complement 3d/genetics , Receptors, Complement 3d/metabolism , SARS-CoV-2 , Virus Replication , Weight Loss
4.
PLoS Pathog ; 18(1): e1010192, 2022 01.
Article in English | MEDLINE | ID: mdl-34995333

ABSTRACT

Candida albicans is a major opportunistic pathogen of humans. It can grow as morphologically distinct yeast, pseudohyphae and hyphae, and the ability to switch reversibly among different forms is critical for its virulence. The relationship between morphogenesis and innate immune recognition is not quite clear. Dectin-1 is a major C-type lectin receptor that recognizes ß-glucan in the fungal cell wall. C. albicans ß-glucan is usually masked by the outer mannan layer of the cell wall. Whether and how ß-glucan masking is differentially regulated during hyphal morphogenesis is not fully understood. Here we show that the endo-1,3-glucanase Eng1 is differentially expressed in yeast, and together with Yeast Wall Protein 1 (Ywp1), regulates ß-glucan exposure and Dectin-1-dependent immune activation of macrophage by yeast cells. ENG1 deletion results in enhanced Dectin-1 binding at the septa of yeast cells; while eng1 ywp1 yeast cells show strong overall Dectin-1 binding similar to hyphae of wild-type and eng1 mutants. Correlatively, hyphae of wild-type and eng1 induced similar levels of cytokines in macrophage. ENG1 expression and Eng1-mediated ß-glucan trimming are also regulated by antifungal drugs, lactate and N-acetylglucosamine. Deletion of ENG1 modulates virulence in the mouse model of hematogenously disseminated candidiasis in a Dectin-1-dependent manner. The eng1 mutant exhibited attenuated lethality in male mice, but enhanced lethality in female mice, which was associated with a stronger renal immune response and lower fungal burden. Thus, Eng1-regulated ß-glucan exposure in yeast cells modulates the balance between immune protection and immunopathogenesis during disseminated candidiasis.


Subject(s)
Candida albicans/pathogenicity , Candidiasis/immunology , Glucan Endo-1,3-beta-D-Glucosidase/metabolism , Virulence/physiology , beta-Glucans/immunology , Animals , Candida albicans/immunology , Candida albicans/metabolism , Candidiasis/metabolism , Female , Male , Mice , Mice, Inbred C57BL , beta-Glucans/metabolism
5.
Plant Biotechnol J ; 21(7): 1465-1478, 2023 07.
Article in English | MEDLINE | ID: mdl-37069831

ABSTRACT

Existing CRISPR/Cas12a-based diagnostic platforms offer accurate and vigorous monitoring of nucleic acid targets, but have the potential to be further optimized for more efficient detection. Here, we profiled 16 Cas12a orthologs, focusing on their trans-cleavage activity and their potential as diagnostic enzymes. We observed the Mb2Cas12a has more robust trans-cleavage activity than other orthologs, especially at lower temperatures. An engineered Mb2Cas12a-RRVRR variant presented robust trans-cleavage activity and looser PAM constraints. Moreover, we found the existing one-pot assay, which simultaneously performed Recombinase Polymerase Amplification (RPA) and Cas12a reaction in one system, resulted in the loss of single-base discrimination during diagnosis. Therefore, we designed a reaction vessel that physically separated the RPA and Cas12a steps while maintaining a closed system. This isolated but closed system made diagnostics more sensitive and specific and effectively prevented contamination. This shelved Mb2Cas12a-RRVRR variant-mediated assay detected various targets in less than 15 min and exhibited equal or greater sensitivity than qPCR when detecting bacterial pathogens, plant RNA viruses and genetically modified crops. Overall, our findings further improved the efficiency of the current CRISPR-based diagnostic system and undoubtedly have great potential for highly sensitive and specific detection of multiple sample types.


Subject(s)
Nucleic Acids , Crops, Agricultural , Plants, Genetically Modified , RNA, Plant , Recombinases/genetics , CRISPR-Cas Systems/genetics
6.
Int J Mol Sci ; 24(16)2023 Aug 11.
Article in English | MEDLINE | ID: mdl-37628891

ABSTRACT

MicroRNAs (miRNAs) are essential regulators of numerous biological processes in animals, including adipogenesis. Despite the abundance of miRNAs associated with adipogenesis, their exact mechanisms of action remain largely unknown. Our study highlights the role of bta-miR-484 as a major regulator of adipocyte proliferation, apoptosis, and differentiation. Here, we demonstrated that the expression of bta-miR-484 initially increased during adipogenesis before decreasing. Overexpression of bta-miR-484 in adipocytes ultimately inhibited cell proliferation and differentiation, reduced the number of EdU fluorescence-stained cells, increased the number of G1 phase cells, reduced the number of G2 and S phase cells, and downregulated the expression of proliferation markers (CDK2 and PCNA) and differentiation markers (CEBPA, FABP4, and LPL). Additionally, overexpression of bta-miR-484 promoted the expression of apoptosis-related genes (Caspase 3, Caspase 9, and BAX), and increased the number of apoptotic cells observed via flow cytometry. In contrast, bta-miR-484 inhibition in adipocytes yielded opposite effects to those observed during bta-miR-484 overexpression. Moreover, luciferase reporter assays confirmed SFRP1 as a target gene of bta-miR-484, and revealed that bta-miR-484 downregulates SFRP1 mRNA expression. These findings offer compelling evidence that bta-miR-484 targets SFRP1, inhibits proliferation and differentiation, and promotes apoptosis. Therefore, these results offer novel insights into the bta-miR-484 regulation of adipocyte growth and development.


Subject(s)
Apoptosis , Genes, cdc , Animals , Cell Differentiation/genetics , Apoptosis/genetics , Adipogenesis/genetics , Cell Proliferation/genetics
7.
Int J Mol Sci ; 24(6)2023 Mar 16.
Article in English | MEDLINE | ID: mdl-36982739

ABSTRACT

Fibroblast growth factor (FGF) family genes are a class of polypeptide factors with similar structures that play an important role in regulating cell proliferation and differentiation, nutritional metabolism, and neural activity. In previous studies, the FGF gene has been widely studied and analyzed in many species. However, the systematic study of the FGF gene in cattle has not been reported. In this study, 22 FGF genes distributed on 15 chromosomes were identified in the Bos taurus genome and clustered into seven subfamilies according to phylogenetic analysis and conservative domains. Collinear analysis showed that the bovine FGF gene family was homologous to Bos grunniens, Bos indicus, Hybrid-Bos taurus, Bubalus bubalis, and Hybrid-Bos indicus, and tandem replication and fragment replication were the key driving forces for the expansion of the gene family. Tissue expression profiling showed that bovine FGF genes were commonly expressed in different tissues, with FGF1, FGF5, FGF10, FGF12, FGF16, FGF17, and FGF20 being highly expressed in adipose tissue. In addition, real-time fluorescence quantitative PCR (qRT-PCR) detection showed that some FGF genes were differentially expressed before and after adipocyte differentiation, indicating their diverse role in the formation of lipid droplets. This study made a comprehensive exploration of the bovine FGF family and laid a foundation for further study on the potential function in the regulation of bovine adipogenic differentiation.


Subject(s)
Fibroblast Growth Factors , Genome , Cattle , Animals , Phylogeny , Fibroblast Growth Factors/genetics , Cell Differentiation/genetics , Buffaloes , Adipocytes
8.
Geriatr Nurs ; 54: 118-128, 2023.
Article in English | MEDLINE | ID: mdl-37782974

ABSTRACT

BACKGROUND: The need for dyadic intervention is enhanced with increasing numbers of older adults with dementia. Studies have shown that sensory art therapies are essential for dementia patients and their caregivers. The effects of dyadic sensory art therapies for people with dementia and their caregivers require further exploration. OBJECTIVES: This review aimed to assess the efficacy of dyadic sensory art therapies on neuropsychiatric symptoms and mental function for dementia patients, caregiver burden and psychological state for caregivers, dyad relationship quality for dyads, and evaluate the potential effects of dyadic sensory art therapies on quality of life for both dementia patients and caregivers. METHODS: An electronic literature search of the PubMed, EMBASE, CINAHL, Web of Science, Cochrane Library, PsycINFO and three Chinese databases (CNKI, Wanfang and CBM) was conducted up to November 2022. Two reviewers (SZ and QG) worked independently to identify relevant studies. Risk of bias was assessed by the Cochrane's and Joanna Briggs Institute's tool. Meta-analyses were conducted using RevMan software 5.4. RESULTS: This systematic review included 15 studies (7 RCTs and 8 quasi-experimental studies). The meta-analysis showed that dyadic sensory art therapies significantly ameliorated neuropsychiatric symptoms (SMD = -0.90, 95% CI -1.61 to -0.20, P = .01), caregiver burden (SMD = -0.75; 95% CI -1.03 to -0.47; P < .001). No significant improvements were found in caregiver depression and quality of life for both patients and caregivers. CONCLUSIONS: Dyadic sensory art therapies are generally effective at ameliorating neuropsychiatric symptoms, and caregiver burden. Future studies are encouraged to design large-scale randomized controlled trials with high-quality study to examine and confirm the effectiveness of dyadic sensory art therapies for these dyads composed of dementia patients and their caregivers. TRIAL REGISTRATION: PROSPERO CRD 42023393577; https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42023393577.


Subject(s)
Dementia , Quality of Life , Humans , Aged , Caregivers/psychology , Dementia/psychology
9.
Gastroenterology ; 160(5): 1647-1661, 2021 04.
Article in English | MEDLINE | ID: mdl-33307034

ABSTRACT

BACKGROUND & AIMS: Gastrointestinal (GI) manifestations have been increasingly reported in patients with coronavirus disease 2019 (COVID-19). However, the roles of the GI tract in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection are not fully understood. We investigated how the GI tract is involved in SARS-CoV-2 infection to elucidate the pathogenesis of COVID-19. METHODS: Our previously established nonhuman primate (NHP) model of COVID-19 was modified in this study to test our hypothesis. Rhesus monkeys were infected with an intragastric or intranasal challenge with SARS-CoV-2. Clinical signs were recorded after infection. Viral genomic RNA was quantified by quantitative reverse transcription polymerase chain reaction. Host responses to SARS-CoV-2 infection were evaluated by examining inflammatory cytokines, macrophages, histopathology, and mucin barrier integrity. RESULTS: Intranasal inoculation with SARS-CoV-2 led to infections and pathologic changes not only in respiratory tissues but also in digestive tissues. Expectedly, intragastric inoculation with SARS-CoV-2 resulted in the productive infection of digestive tissues and inflammation in both the lung and digestive tissues. Inflammatory cytokines were induced by both types of inoculation with SARS-CoV-2, consistent with the increased expression of CD68. Immunohistochemistry and Alcian blue/periodic acid-Schiff staining showed decreased Ki67, increased cleaved caspase 3, and decreased numbers of mucin-containing goblet cells, suggesting that the inflammation induced by these 2 types of inoculation with SARS-CoV-2 impaired the GI barrier and caused severe infections. CONCLUSIONS: Both intranasal and intragastric inoculation with SARS-CoV-2 caused pneumonia and GI dysfunction in our rhesus monkey model. Inflammatory cytokines are possible connections for the pathogenesis of SARS-CoV-2 between the respiratory and digestive systems.


Subject(s)
COVID-19/transmission , Gastroenteritis/pathology , Gastrointestinal Tract/pathology , Lung/pathology , Animals , Bronchi/metabolism , Bronchi/pathology , COVID-19/immunology , COVID-19/metabolism , COVID-19/pathology , COVID-19 Nucleic Acid Testing , Caspase 3/metabolism , Cytokines/immunology , Disease Models, Animal , Gastric Mucosa , Gastroenteritis/metabolism , Gastroenteritis/virology , Gastrointestinal Tract/immunology , Gastrointestinal Tract/metabolism , Goblet Cells/pathology , Intestine, Small/metabolism , Intestine, Small/pathology , Ki-67 Antigen/metabolism , Lung/diagnostic imaging , Lung/immunology , Lung/metabolism , Macaca mulatta , Nasal Mucosa , RNA, Viral/isolation & purification , Random Allocation , Rectum/metabolism , Rectum/pathology , SARS-CoV-2 , Trachea/metabolism , Trachea/pathology
11.
J Nanobiotechnology ; 20(1): 260, 2022 Jun 07.
Article in English | MEDLINE | ID: mdl-35672856

ABSTRACT

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), seriously threatens human life and health. The correct folding and polymerization of the receptor-binding domain (RBD) protein of coronavirus in Escherichia coli may reduce the cost of SARS-CoV-2 vaccines. In this study, we constructed this nanopore by using the principle of ClyA porin polymerization triggered by the cell membrane. We used surfactants to "pick" the ClyA-RBD nanopore from the bacterial outer membrane. More importantly, the polymerized RBD displayed on the ClyA-RBD polymerized porin (RBD-PP) already displays some correct spatial conformational epitopes that can induce neutralizing antibodies. The nanostructures of RBD-PP can target lymph nodes and promote antigen uptake and processing by dendritic cells, thereby effectively eliciting the production of anti-SARS-CoV-2 neutralizing antibodies, systemic cellular immune responses, and memory T cells. We applied this PP-based vaccine platform to fabricate an RBD-based subunit vaccine against SARS-CoV-2, which will provide a foundation for the development of inexpensive coronavirus vaccines. The development of a novel vaccine delivery system is an important part of innovative drug research. This novel PP-based vaccine platform is likely to have additional applications, including other viral vaccines, bacterial vaccines, tumor vaccines, drug delivery, and disease diagnosis.


Subject(s)
COVID-19 Vaccines , COVID-19 , Antibodies, Neutralizing , Antibodies, Viral/metabolism , COVID-19/prevention & control , Humans , Polymerization , Porins , SARS-CoV-2 , Spike Glycoprotein, Coronavirus
12.
Nanomedicine ; 41: 102527, 2022 04.
Article in English | MEDLINE | ID: mdl-35104670

ABSTRACT

New SARS-COV-2 vaccine strategies are still urgently needed, especially for emerging virus mutations and variants. In this study, we focused on analyzing the antigenicity and vaccine potency of linear peptide epitopes located in receptor binding motif (RBM) of spike (S) protein. Nine 12 to 16-mer overlapping peptides (P1-P9) were synthesized chemically and coupled to carrier protein KLH for the immunization in mice. Four of identified peptides were further engineered to present on the surface of recombinant Hepatitis B core antigen (HBcAg) virus-like particles (VLPs) respectively. Antisera obtained from VLPs -immunized mice demonstrated strong reactivity and affinity to S1 protein or inactivated virus and neutralizing activity against virus infection in vitro. This study indicates that recombinant VLPs empower peptides which display underprivileged antigenicity in native protein to elicit high levels of neutralizing antibody, providing potential epitope candidates and an effective delivery strategy for the development of a multi-epitope vaccine.


Subject(s)
Antibodies, Neutralizing , COVID-19 , Animals , Antibodies, Viral , COVID-19/prevention & control , COVID-19 Vaccines , Humans , Mice , Peptides/genetics , SARS-CoV-2 , Spike Glycoprotein, Coronavirus/genetics
13.
Nano Lett ; 21(14): 5920-5930, 2021 07 28.
Article in English | MEDLINE | ID: mdl-34279108

ABSTRACT

The disease caused by SARS-CoV-2 infection threatens human health. In this study, we used high-pressure homogenization technology not only to efficiently drive the bacterial membrane to produce artificial vesicles but also to force the fusion protein ClyA-receptor binding domain (RBD) to pass through gaps in the bacterial membrane to increase the contact between ClyA-RBD and the membrane. Therefore, the load of ClyA-RBD on the membrane is substantially increased. Using this technology, we constructed a "ring-like" bacterial biomimetic vesicle (BBV) loaded with polymerized RBD (RBD-BBV). RBD-BBVs injected subcutaneously can accumulate in lymph nodes, promote antigen uptake and processing, and elicit SARS-CoV-2-specific humoral and cellular immune responses in mice. In conclusion, we evaluated the potential of this novel bacterial vesicle as a vaccine delivery system and provided a new idea for the development of SARS-CoV-2 vaccines.


Subject(s)
COVID-19 , Spike Glycoprotein, Coronavirus , Animals , COVID-19 Vaccines , Humans , Mice , Protein Binding , SARS-CoV-2
14.
J Anim Physiol Anim Nutr (Berl) ; 106(6): 1197-1207, 2022 Nov.
Article in English | MEDLINE | ID: mdl-34791721

ABSTRACT

The proliferation and differentiation of pre-adipocytes are regulated by microRNAs (miRNAs) and other factors. In this study, the potential functions of bta-miR-6517 in the regulation of pre-adipocyte proliferation and differentiation were explored. The qRT-PCR, oil red O staining and CCK-8 assay were used to evaluate the role of bta-miR-6517. Further, the target gene of bta-miR-6517 was identified using bioinformatics analysis, dual-luciferase reporter system and qRT-PCR system. The results found that the overexpression of bta-miR-6517 promoted the expression of proliferation marker genes and substantially increased the adipocyte proliferation vitality in the CCK-8 assay, whereas suppressing of bta-miR-6517 had the opposite effect. Overexpression bta-miR-6517 suppressed the expression of adipogenic genes, which inhibited lipid accumulation, whereas suppressing of bta-miR-6517 had the opposite effect. Furthermore, the dual-fluorescent reporter experiment results demonstrated that bta-miR-6517 directly targeted phosphofructokinase, liver type (PFKL). When bta-miR-6517 was either overexpressed or suppressed, it negatively regulated PFKL. In conclusion, we observed that bta-miR-6517 promoted adipocyte proliferation and inhibited differentiation by targeting PFKL.


Subject(s)
MicroRNAs , Phosphofructokinases , Animals , Phosphofructokinases/metabolism , Adipocytes , MicroRNAs/genetics , Cell Proliferation , Liver/metabolism , Cell Differentiation
15.
Reproduction ; 162(4): 249-257, 2021 09 06.
Article in English | MEDLINE | ID: mdl-34314375

ABSTRACT

The specificity of sperm-egg recognition is crucial to species independence, and two proteins (Izumo1 and JUNO) are essential for gamete adhesion/fusion in mammals. However, hybridization, which is very common in turtles, also requires specific recognition of sperm-egg binding proteins. In this study, we discovered that natural selection plays an important role in the codon usage bias of Tu-Izumo1 and Tu-JUNO. Positively selected sites and co-evolutionary analyses between Tu-Izumo1 and Tu-JUNO have been previously reported, and we confirm these results in a larger analysis containing 25 turtle species. We also showed that Tu-JUNO is expressed on the oocyte surface and that Tu-Izumo1 and Tu-JUNO interact with each other directly in different species hybridization combinations. Co-immunization assays revealed that this interaction is evolutionarily conserved in turtles. The results of avidity-based extracellular interaction screening between Tu-Izumo1 and Tu-JUNO for sperm-oocyte binding pairs (both within and across species) likely suggest that the interaction force between Izumo1 and JUNO has a certain correlation in whether the turtles can hybridize. Our results lay a theoretical foundation for the subsequent development of techniques to detect whether different turtle species can interbreed, which would provide the molecular basis for breeding management and species protection of turtles.


Subject(s)
Sperm-Ovum Interactions , Turtles , Animals , Immunoglobulins/metabolism , Membrane Proteins/genetics , Membrane Proteins/metabolism , Receptors, Cell Surface/metabolism , Turtles/genetics , Turtles/metabolism
16.
Biochem Biophys Res Commun ; 508(3): 980-985, 2019 01 15.
Article in English | MEDLINE | ID: mdl-30551880

ABSTRACT

Growing evidence indicates that circular RNA (circRNA) plays an important role in the regulation of tumor biological behaviors. In this study, we aimed to explore the role of a novel circRNA, circ_0034642, in glioma. qRT-PCR was conducted to evaluate the levels of circ_0034642 in glioma tissues and cells. In addition, the clinical severity and prognostic role of circ_0034642 were illustrated. Functionally, loss and gain-of function assays were performed by CCK-8, colony-forming, flow cytometric and transwell experiments in glioma cells. Moreover, luciferase reporter assay was used to detect the mechanism of circ_0034642. Circ_0034642 was upregulated in glioma tissues and cell lines. Overexpressed circ_0034642 was correlated with adverse phenotypes in the patients with glioma. In addition, circ_0034642 could be regarded as a prognostic predictor for glioma patients. Moreover, circ_0034642 could promote cell proliferation, migratory and invasive capacities and inhibit cell apoptosis. For the mechanism investigation, circ_0034642 was proved to be a sponge of miR-1205, and miR-1205 could regulate BATF3 expression via targeting 3'UTR of BATF3. Rescue assays also illustrated that the oncogenic function of circ_0034642 is partly attributed to its modulation on miR-1205/BATF3 axis. Collectively, circ_0034642/miR-1205/BATF3 pathway may play an important role in glioma.


Subject(s)
Basic-Leucine Zipper Transcription Factors/genetics , Brain Neoplasms/genetics , Glioma/genetics , MicroRNAs/genetics , RNA/metabolism , Repressor Proteins/genetics , Adult , Apoptosis , Basic-Leucine Zipper Transcription Factors/metabolism , Brain Neoplasms/metabolism , Brain Neoplasms/pathology , Cell Line, Tumor , Cell Proliferation , Female , Glioma/metabolism , Glioma/pathology , Glioma/secondary , Humans , Male , Middle Aged , Neoplasm Invasiveness , RNA, Circular , Repressor Proteins/metabolism , Signal Transduction
17.
Mol Carcinog ; 58(11): 2065-2076, 2019 11.
Article in English | MEDLINE | ID: mdl-31432570

ABSTRACT

Colorectal cancer (CRC) is one of the most common malignant tumors worldwide. As tumor metastasis is the leading cause of death in patients with CRC, it is important to elucidate the molecular mechanisms that drive CRC metastasis. Studies have shown a close relationship between Iroquois homeobox (IRX) family genes and multiple cancers, while the mechanism by which IRX5 promotes CRC metastasis is unclear. Therefore, we focused on the involvement of IRX5 in CRC metastasis. In this study, analyses of clinical data indicated that the expression of IRX5 was coincided with metastatic colorectal tumors tissues and was negatively correlated with the overall survival of patients with CRC. Functional analysis showed that IRX5 promoted the migration and invasion of CRC cells, accompanied by a large number of cellular protrusions. IRX5-overexpressing cells were more likely to form metastatic tumors in nude mice. Further analysis demonstrated that the core components of the RHOA/ROCK1/LIMK1 pathway were significantly inhibited in IRX5-overexpressing cells. Overexpression of LIMK1 effectively reversed the enhanced cellular motility caused by IRX5 overexpression. Moreover, we found that high levels of IRX5 in intestinal tissues were correlated with the inflammatory response. IRX5 was significantly increased in azoxymethane/dextran sodium sulfate intestinal tissue of mice and IRX5-overexpressing may also enhance chemokines CXCL1 and CXCL8. In summary, our findings suggested that IRX5 promoted CRC metastasis by inhibiting the RHOA-ROCK1-LIMK1 axis, which correlates with a poor prognosis.


Subject(s)
Colorectal Neoplasms/genetics , Homeodomain Proteins/genetics , Inflammation/genetics , Transcription Factors/genetics , rhoA GTP-Binding Protein/genetics , Animals , Chemokine CXCL1/genetics , Colorectal Neoplasms/pathology , Epithelial-Mesenchymal Transition/genetics , Female , Gene Expression Regulation, Neoplastic/genetics , HT29 Cells , Heterografts , Humans , Interleukin-8/genetics , Intestines/pathology , Lim Kinases/genetics , Male , Mice , Neoplasm Metastasis , Signal Transduction/drug effects , Tissue Array Analysis , rho-Associated Kinases/genetics
18.
Ecotoxicol Environ Saf ; 167: 107-113, 2019 Jan 15.
Article in English | MEDLINE | ID: mdl-30312888

ABSTRACT

Previous researches have reported that microcystin-LR (MC-LR) contributes to the progression of multiple types of carcinomas including colon cancer; however, the underlying molecular mechanisms remain unclear and require in-depth investigation. Here, the colon cell line DLD-1 was arranged for the analysis by the microRNA microarray which was associated with the cancer metastasis after MC-LR exposure. 31 human microRNAs were differentially expressed, including miR-221, which targeted 3'-UTR of PTEN mRNA and PTEN level was down-regulated by MC-LR treatment. Besides, MC-LR also induced the phosphorylation of STAT3, which can be reversed by adding miR-221 inhibitor and PTEN expression plasmid. Furthermore, miR-221 inhibitor, STAT3 siRNA and PTEN expression plasmid could reverse the effects of MC-LR induced migration with the accumulation of ß-catenin in nuclei. In conclusion, our study suggested that MC-LR promoted the progression of colon carcinoma, at least in part, by regulating the expression miR-221, PTEN and STAT3 phosphorylation, which offers a novel perspective to understand the connection between MC-LR and colon cancer.


Subject(s)
Colonic Neoplasms/genetics , Enzyme Inhibitors/pharmacology , MicroRNAs/genetics , Microcystins/pharmacology , PTEN Phosphohydrolase/genetics , STAT3 Transcription Factor/genetics , Cell Line, Tumor , Cell Movement/drug effects , Colonic Neoplasms/metabolism , Colonic Neoplasms/pathology , Down-Regulation , Humans , Marine Toxins , MicroRNAs/antagonists & inhibitors , PTEN Phosphohydrolase/metabolism , Phosphorylation/drug effects , RNA, Messenger/metabolism , RNA, Small Interfering , STAT3 Transcription Factor/metabolism , Signal Transduction/drug effects , Up-Regulation , beta Catenin/metabolism
19.
Angew Chem Int Ed Engl ; 57(7): 1893-1897, 2018 02 12.
Article in English | MEDLINE | ID: mdl-29272059

ABSTRACT

Mechanofluorochromic materials, which change their photoluminescence (PL) colors in responding to mechanical stimuli, can be used as mechanosensors, security papers, and photoelectronic devices. However, traditional mechanofluorochromic materials can only be adjusted to a monotone direction upon the external stimuli. Controllable pressure-triggered blue- and red-shifted PL is reported for C-dots. The origin of mechanofluorochromism (MFC) in C-dots is interpreted based on structure-property relationships. The carbonyl group and the π-conjugated system play key roles in the PL change of C-dots under high pressure. As the pressure increases, the enhanced π-π stacking of the π-conjugated system causes the red-shift of PL, while the conversion of carbonyl groups eventually induces a blue-shift. Together with their low toxicity, good hydrophilicity, and small size, the tunable MFC property would boost various potential applications of C-dots.

20.
Guang Pu Xue Yu Guang Pu Fen Xi ; 35(3): 631-4, 2015 Mar.
Article in Zh | MEDLINE | ID: mdl-26117869

ABSTRACT

The silicate nickel ores developed in the lateritic nickel deposit, from Kolonodale, Sulawesi Island, Indonesia, and Yuanjiang, Yunnan province, China, were selected for the present study. The X-ray diffraction and Fourier infrared spectra were used to analyze the mineralogical attribute of laterite nickel ores from two different places. The results show that these two different silicate nickel ores have unique infrared spectra characteristics individually, which contributes to the ore classification. The silicate nickel ores from Kolonodale deposit, Indonesia, can be classified as the serpentine type, the montmorillonite + serpentine type, and the garnierite type. While, the silicate nickel ores from Yuanjiang deposit, China, can be classified as the serpentine type and the talc + serpentine type. Moreover, the mineral crystallinity of Yuanjiang nickel ores is generally better than Kolonodale nickel ores. According to the advantage of infrared absorption spectra in distinguishing mineral polytypes, it can be determined that lizardite is the main mineral type in the silicate nickel ores of the two deposits, and there is no obvious evidence of chrysotile and antigorite's existence. The characteristic of infrared absorption spectra also shows that frequency change of OH libration indicates Ni (Fe) replacing Mg in the serpentine type nickel-bearing mineral, that is, OH libration of serpentine moves to higher frequency, with the proportion of Ni (Fe) replacing Mg increasing.

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