ABSTRACT
The osteoimmune microenvironment induced by implants plays a significant role in bone regeneration. It is essential to efficiently and timely switch the macrophage phenotype from M1 to M2 for optimal bone healing. This study examined the impact of a calcium phosphate (CaP) coating on the physiochemical properties of highly ordered polycaprolactone (PCL) scaffolds fabricated using melt electrowritten (MEW). Additionally, it investigated the influence of these scaffolds on macrophage polarization and their immunomodulation on osteogenesis. The results revealed that the CaP coated PCL scaffold exhibited a rougher surface topography and higher hydrophilicity in comparison to the PCL scaffold without coating. Besides, the surface morphology of the coating and the release of Ca2+ from the CaP coating were crucial in regulating the transition of macrophages from M1 to M2 phenotypes. They might activate the PI3K/AKT and cAMP-PKA pathways, respectively, to facilitate M2 polarization. In addition, the osteoimmune microenvironment induced by CaP coated PCL could not only enhance the osteogenic differentiation of bone marrow-derived mesenchymal stem cells (BMSCs) in vitro but also promote the bone regeneration in vivo. Taken together, the CaP coating can be employed to control the phenotypic switching of macrophages, thereby creating a beneficial immunomodulatory microenvironment that promotes bone regeneration.
Subject(s)
Osteogenesis , Tissue Scaffolds , Tissue Scaffolds/chemistry , Phosphatidylinositol 3-Kinases/metabolism , Bone Regeneration , Macrophages/metabolism , Calcium Phosphates/chemistryABSTRACT
The erythropoietin receptor (EpoR) has traditionally been thought of as an erythroid-specific gene. Notably, accumulating evidence suggests that EpoR is expressed well beyond erythroid cells. However, the expression of EpoR in non-erythroid cells has been controversial. In this study, we generated EpoR-tdTomato-Cre mice and used them to examine the expression of EpoR in tissue macrophages and hematopoietic cells. We show that in marked contrast to the previously available EpoR-eGFPcre mice, in which a very weak eGFP signal was detected in erythroid cells, tdTomato was readily detectable in both fetal liver (FL) and bone marrow (BM) erythroid cells at all developmental stages and exhibited dynamic changes during erythropoiesis. Consistent with our recent finding that erythroblastic island (EBI) macrophages are characterized by the expression of EpoR, tdTomato was readily detected in both FL and BM EBI macrophages. Moreover, tdTomato was also detected in subsets of hematopoietic stem cells, progenitors, megakaryocytes, and B cells in BM as well as in spleen red pulp macrophages and liver Kupffer cells. The expression of EpoR was further shown by the EpoR-tdTomato-Cre-mediated excision of the floxed STOP sequence. Importantly, EPO injection selectively promoted proliferation of the EpoR-expressing cells and induced erythroid lineage bias during hematopoiesis. Our findings imply broad roles for EPO/EpoR in hematopoiesis that warrant further investigation. The EpoR-tdTomato-Cre mouse line provides a powerful tool to facilitate future studies on EpoR expression and regulation in various non-hematopoietic cells and to conditionally manipulate gene expression in EpoR-expressing cells for functional studies.
Subject(s)
Gene Expression , Hematopoietic Stem Cells/metabolism , Macrophages/metabolism , Receptors, Erythropoietin/genetics , Animals , Hematopoietic Stem Cells/cytology , Humans , Integrases/analysis , Integrases/genetics , Luminescent Agents/analysis , Luminescent Agents/metabolism , Luminescent Proteins/analysis , Luminescent Proteins/genetics , Macrophages/cytology , Mice , Receptors, Erythropoietin/analysis , Red Fluorescent ProteinABSTRACT
Histone deacetylases (HDACs) are a group of enzymes that catalyze the removal of acetyl groups from histone and nonhistone proteins. HDACs have been shown to have diverse functions in a wide range of biological processes. However, their roles in mammalian erythropoiesis remain to be fully defined. This study showed that, of the 11 classic HDAC family members, 6 (HDAC1, -2, -3, and HDAC5, -6, -7) are expressed in human erythroid cells, with HDAC5 most significantly upregulated during terminal erythroid differentiation. Knockdown of HDAC5 by either short hairpin RNA or small interfering RNA in human CD34+ cells followed by erythroid cell culture led to increased apoptosis, decreased chromatin condensation, and impaired enucleation of erythroblasts. Biochemical analyses revealed that HDAC5 deficiency resulted in activation of p53 in association with increased acetylation of p53. Furthermore, although acetylation of histone 4 (H4) is decreased during normal terminal erythroid differentiation, HDAC5 deficiency led to increased acetylation of H4 (K12) in late-stage erythroblasts. This increased acetylation was accompanied by decreased chromatin condensation, implying a role for H4 (K12) deacetylation in chromatin condensation. ATAC-seq and RNA sequencing analyses revealed that HDAC5 knockdown leads to increased chromatin accessibility genome-wide and global changes in gene expression. Moreover, pharmacological inhibition of HDAC5 by the inhibitor LMK235 also led to increased H4 acetylation, impaired chromatin condensation, and enucleation. Taken together, our findings have uncovered previously unrecognized roles and molecular mechanisms of action for HDAC5 in human erythropoiesis. These results may provide insights into understanding the anemia associated with HDAC inhibitor treatment.
Subject(s)
Erythroid Cells/cytology , Erythropoiesis , Histone Deacetylases/genetics , Apoptosis , Erythroblasts/cytology , Erythroblasts/metabolism , Erythroid Cells/metabolism , Humans , RNA Interference , RNA, Small Interfering/genetics , Up-RegulationABSTRACT
Enhancer of zeste homolog 2 (EZH2) is the lysine methyltransferase of polycomb repressive complex 2 (PRC2) that catalyzes H3K27 tri-methylation. Aberrant expression and loss-of-function mutations of EZH2 have been demonstrated to be tightly associated with the pathogenesis of various myeloid malignancies characterized by ineffective erythropoiesis, such as myelodysplastic syndrome (MDS). However, the function and mechanism of EZH2 in human erythropoiesis still remains largely unknown. Here, we demonstrated that EZH2 regulates human erythropoiesis in a stage-specific, dual-function manner by catalyzing histone and non-histone methylation. During the early erythropoiesis, EZH2 deficiency caused cell cycle arrest in the G1 phase, which impaired cell growth and differentiation. Chromatin immunoprecipitation sequencing and RNA sequencing discovered that EZH2 knockdown caused a reduction of H3K27me3 and upregulation of cell cycle proteindependent kinase inhibitors. In contrast, EZH2 deficiency led to the generation of abnormal nuclear cells and impaired enucleation during the terminal erythropoiesis. Interestingly, EZH2 deficiency downregulated the methylation of HSP70 by directly interacting with HSP70. RNA-sequencing analysis revealed that the expression of AURKB was significantly downregulated in response to EZH2 deficiency. Furthermore, treatment with an AURKB inhibitor and small hairpin RNAmediated AURKB knockdown also led to nuclear malformation and decreased enucleation efficiency. These findings strongly suggest that EZH2 regulates terminal erythropoiesis through a HSP70 methylation-AURKB axis. Our findings have implications for improved understanding of ineffective erythropoiesis with EZH2 dysfunction.
Subject(s)
Enhancer of Zeste Homolog 2 Protein , Erythropoiesis , Histones , Humans , Enhancer of Zeste Homolog 2 Protein/genetics , Erythropoiesis/genetics , Histones/metabolism , Methylation , Polycomb Repressive Complex 2/genetics , Polycomb Repressive Complex 2/metabolismABSTRACT
BACKGROUND: Cervical cancer is the most common gynecological cancer worldwide and is associated with high morbidity and mortality. Despite improvements in therapeutic strategies, the network regulation mechanism remains unclear and the treatment effect is not satisfactory. Therefore, there is a need to continue studying the mechanism of cervical cancer to explore effective gene targets and precise targeted therapy drugs. METHODS: First, three paired tissues (cancer tissues and noncancerous tissues) from patients with cervical squamous cell carcinoma were collected, grouped, and analyzed by microarray. Second, differentially expressed mRNAs (DEMs) and differentially expressed lncRNAs (DELs) (|fold change| ≥ 2 and p < 0.05) between the two groups were screened. For DEMs, functional annotation and pathway analysis were performed using DAVID. Functional prediction of DELs was then performed and their cis-regulatory and trans-regulatory networks were explored. RESULTS: Function prediction of DELs (both up-regulated and down-regulated) shows that the highest frequency Cellular Component (CC) item is cytosol, the highest frequency Molecular function (MF) item is mitotic cell cycle and the highest frequency Biological Process (BP) item is protein binding. Through cis-regulation analysis of DELs, the cis-regulatory relationship of 96 DELs was predicted. The lncRNA-trans-regulation network analysis suggested that E2F4 may be the core transcription factor in the lncRNA-TF regulatory network in cervical cancer. CONCLUSIONS: The lncRNA-TF regulatory network plays an important role in the occurrence and progression of cervical cancer, and E2F4 may be a critical transcription factor in the regulatory network.
Subject(s)
MicroRNAs , RNA, Long Noncoding , Uterine Cervical Neoplasms , E2F4 Transcription Factor/genetics , E2F4 Transcription Factor/metabolism , Female , Gene Expression Regulation, Neoplastic , Gene Regulatory Networks/genetics , Humans , MicroRNAs/genetics , RNA, Long Noncoding/genetics , RNA, Long Noncoding/metabolism , RNA, Messenger/metabolism , Transcription Factors/genetics , Uterine Cervical Neoplasms/geneticsABSTRACT
PURPOSE: To identify the recurrence rate and risk factors for recurrence in patients with juvenile-onset recurrent respiratory papillomatosis (JORRP). METHODS: A retrospective review was performed for all JORRP patients who underwent surgery between 2002 and 2019 at our institution. The demographic characteristics and clinical parameters were recorded. Kaplan-Meier estimates and Cox proportional hazards models were used to analyze the rate of recurrence and its risk factors. RESULTS: Our study included 721 patients. The cumulative recurrence rates at 1, 5, and 10 postoperative years following initial surgery were 74.2%, 90.0%, and 94.3%, respectively. Age at diagnosis younger than 4.5 years (HR = 2.380, 95% CI [1.169-4.846], P = 0.017), high Derkay anatomical score (HR = 1.136, 95% CI [1.043-1.236], P = 0.003) and HPV type 11 infection (HR = 2.947, 95% CI [1.326-6.551], P = 0.008) were independent risk factors for recurrence. Adjuvant therapy with interferon was less likely to recur (HR = 0.237, 95% CI [0.091-0.616], P = 0.003). Additionally, gender, tracheotomy, mode of delivery, parity, expression of Ki-67, HPV vaccination, and surgical treatment method were not independently associated with recurrence (P > 0.05). CONCLUSION: Age at diagnosis younger than 4.5 years, high Derkay anatomical score and HPV type 11 infection were associated with an increased risk for recurrence in patients with JORRP. Adjuvant therapy with interferon may reduce the risk of recurrence.
Subject(s)
Papillomavirus Infections , Respiratory Tract Infections , Antiviral Agents/therapeutic use , Female , Humans , Interferons/therapeutic use , Papillomavirus Infections/diagnosis , Papillomavirus Infections/epidemiology , Pregnancy , Respiratory Tract Infections/epidemiology , Respiratory Tract Infections/surgery , Retrospective Studies , Risk FactorsABSTRACT
Myelodysplastic syndromes (MDSs) are clonal hematopoietic stem cell disorders characterized by ineffective hematopoiesis. Anemia is the defining cytopenia of MDS patients, yet the molecular mechanisms for dyserythropoiesis in MDSs remain to be fully defined. Recent studies have revealed that heterozygous loss-of-function mutation of DNA dioxygenase TET2 is 1 of the most common mutations in MDSs and that TET2 deficiency disturbs erythroid differentiation. However, mechanistic insights into the role of TET2 on disordered erythropoiesis are not fully defined. Here, we show that TET2 deficiency leads initially to stem cell factor (SCF)-dependent hyperproliferation and impaired differentiation of human colony-forming unit-erythroid (CFU-E) cells, which were reversed by a c-Kit inhibitor. We further show that this was due to increased phosphorylation of c-Kit accompanied by decreased expression of phosphatase SHP-1, a negative regulator of c-Kit. At later stages, TET2 deficiency led to an accumulation of a progenitor population, which expressed surface markers characteristic of normal CFU-E cells but were functionally different. In contrast to normal CFU-E cells that require only erythropoietin (EPO) for proliferation, these abnormal progenitors required SCF and EPO and exhibited impaired differentiation. We termed this population of progenitors "marker CFU-E" cells. We further show that AXL expression was increased in marker CFU-E cells and that the increased AXL expression led to increased activation of AKT and ERK. Moreover, the altered proliferation and differentiation of marker CFU-E cells were partially rescued by an AXL inhibitor. Our findings document an important role for TET2 in erythropoiesis and have uncovered previously unknown mechanisms by which deficiency of TET2 contributes to ineffective erythropoiesis.
Subject(s)
DNA-Binding Proteins/genetics , Erythroid Precursor Cells/pathology , Loss of Function Mutation , Myelodysplastic Syndromes/genetics , Proto-Oncogene Proteins/genetics , Cell Line, Tumor , Cell Proliferation , DNA Methylation , Dioxygenases , Erythroid Precursor Cells/cytology , Erythroid Precursor Cells/metabolism , Erythropoiesis , Gene Deletion , Gene Knockdown Techniques , Humans , Myelodysplastic Syndromes/pathology , Proto-Oncogene Proteins c-kit/genetics , Up-RegulationABSTRACT
PURPOSE: The aim of this study was to investigate the effects of maternal high dietary protein intake on the hepatic growth axis in offspring. METHODS: Fourteen primiparous purebred Meishan sows were fed either a standard-protein (SP, n = 7) diet or a high-protein (HP, 150% of SP, n = 7) diet during pregnancy. Offspring (one male and one female per group, n = 14) on day 70 of the embryonic stage and on days 1, 35 and 180 after birth were selected, weighed and killed. Serum samples were analyzed for Tch, insulin and insulin-like growth factor-binding protein 3 (IGFBP-3) levels. Liver samples were analyzed for IGFBP-3 and IGF-I mRNA expression by qRT-PCR and for IGFBP-3, IGF1R and growth hormone receptor (GHR) protein expression by Western blotting. The underlying mechanism of IGFBP-3 regulation was determined by methylated DNA immunoprecipitation (MeDIP) and chromatin immunoprecipitation (ChIP). RESULTS: High-protein exposure resulted in significantly higher body and liver weights of piglets, and it increased their serum T3 and T4 levels at birth and/or at weaning. Furthermore, the IGFBP-3 protein content in the liver and serum was significantly reduced in the HP-exposed weaning piglets, whereas at the transcriptional level IGFBP-3 mRNA expression was downregulated in the livers of HP group piglets. Finally, DNA hypermethylation and higher enrichment of the histone repressive marks H3K27me3 and H3K9me3 were observed. CONCLUSIONS: Taken together, these results suggest that a maternal high-protein diet during gestation epigenetically reprograms IGFBP-3 gene expression to modulate the hepatic growth axis in weaning piglets.
Subject(s)
Diet, High-Protein , Epigenesis, Genetic , Insulin-Like Growth Factor Binding Protein 3/genetics , Liver/growth & development , Mothers , Swine/growth & development , Swine/physiology , Animals , DNA Methylation , Female , Insulin-Like Growth Factor I/genetics , Liver/metabolism , Male , Pregnancy , WeaningABSTRACT
U2AF1 (U2AF35) is the small subunit of the U2 auxiliary factor (U2AF) that constitutes the U2 snRNP (small nuclear ribonucleoproteins) of the spliceosome. Here, we examined the function of U2AF1 in human erythropoiesis. First, we examined the expression of U2AF1 during in vitro human erythropoiesis and showed that U2AF1 was highly expressed in the erythroid progenitor burst-forming-unit erythroid (BFU-E) cell stage. A colony assay revealed that U2AF1 knockdown cells failed to form BFU-E and colony-forming-unit erythroid (CFU-E) colonies. Our results further showed that knockdown of U2AF1 significantly inhibited cell growth and induced apoptosis in erythropoiesis. Additionally, knockdown of U2AF1 also delayed terminal erythroid differentiation. To explore the molecular basis of the impaired function of erythroid development, RNA-seq was performed and the Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis results showed that several biological pathways, including the p53 signalling pathway, MAPK signalling pathway and haematopoietic cell lineage, were involved, with the p53 signalling pathway showing the greatest involvement. Western blot analysis revealed an increase in the protein levels of downstream targets of p53 following U2AF1 knockdown. The data further showed that depletion of U2AF1 altered alternatively spliced apoptosis-associated gene transcripts in CFU-E cells. Our findings elucidate the role of U2AF1 in human erythropoiesis and reveal the underlying mechanisms.
Subject(s)
Cell Proliferation/genetics , Erythroid Precursor Cells/metabolism , Erythropoiesis/genetics , Splicing Factor U2AF/genetics , Erythroid Precursor Cells/cytology , Gene Expression Regulation, Developmental , Gene Knockdown Techniques , Humans , Mitogen-Activated Protein Kinase Kinases/genetics , RNA-Seq , Signal Transduction/genetics , Spliceosomes/genetics , Tumor Suppressor Protein p53/geneticsABSTRACT
Lactic acid (LA) is a powerful molecule as the metabolic driver in tumor microenvironments (TMEs). Inspired by its high intratumoral level (5-20 µmol g-1 ), a novel treatment paradigm via the cascade release of H2 O2 and ·OH from the LA generated by tumor metabolism is developed for catalytic and pH-dependent selective tumor chemotherapy. By utilizing the acidity and overexpression of LA within the TME, the constructed lactate oxidase (LOD)-immobilized Ce-benzenetricarboxylic acid (Ce-BTC) metal organic framework enables the intratumoral generation of ·OH via a cascade reaction: 1) the in situ catalytic release of H2 O2 from LA by LOD, and 2) the catalytic production of ·OH from H2 O2 by Ce-BTC with peroxidase-like activity. Highly toxic ·OH effectively induces tumor apoptosis/death. A new strategy for selective tumor chemotherapy is provided herein.
Subject(s)
Lactic Acid/metabolism , Neoplasms/drug therapy , Neoplasms/metabolism , Animals , Antineoplastic Agents/pharmacology , Antineoplastic Agents/therapeutic use , Catalysis , Cell Death , Cerium/chemistry , Enzymes, Immobilized/metabolism , Hep G2 Cells , Humans , Mice, Inbred BALB C , Mice, Nude , Mixed Function Oxygenases/metabolism , Tricarboxylic Acids/chemistryABSTRACT
The ten-eleven translocation (TET) family of proteins plays important roles in a wide range of biological processes by oxidizing 5-methylcytosine (5mC) to 5-hydroxy-methylcytosine. However, their function in erythropoiesis has remained unclear. We show here that TET2 and TET3 but not TET1 are expressed in human erythroid cells, and we explore the role of these proteins in erythropoiesis. Knockdown experiments revealed that TET2 and TET3 have different functions. Suppression of TET3 expression in human CD34+ cells markedly impaired terminal erythroid differentiation, as reflected by increased apoptosis, the generation of bi/multinucleated polychromatic/orthochromatic erythroblasts, and impaired enucleation, although without effect on erythroid progenitors. In marked contrast, TET2 knockdown led to hyper-proliferation and impaired differentiation of erythroid progenitors. Surprisingly, knockdown of neither TET2 nor TET3 affected global levels of 5mC. Thus, our findings have identified distinct roles for TET2 and TET3 in human erythropoiesis, and provide new insights into their role in regulating human erythroid differentiation at distinct stages of development. Moreover, because knockdown of TET2 recapitulates certain features of erythroid development defects characteristic of myelodysplastic syndromes (MDSs), and the TET2 gene mutation is one of the most common mutations in MDS, our findings may be relevant for improved understanding of dyserythropoiesis of MDS.
Subject(s)
DNA-Binding Proteins/metabolism , Dioxygenases/metabolism , Erythropoiesis/physiology , Hematopoietic Stem Cells/metabolism , Proto-Oncogene Proteins/metabolism , Antigens, CD34/genetics , Antigens, CD34/metabolism , DNA-Binding Proteins/genetics , Dioxygenases/genetics , Gene Knockdown Techniques , Hematopoietic Stem Cells/cytology , Humans , Mixed Function Oxygenases/genetics , Mixed Function Oxygenases/metabolism , Myelodysplastic Syndromes/genetics , Myelodysplastic Syndromes/metabolism , Proto-Oncogene Proteins/geneticsABSTRACT
This paper discusses synthesis and application of dual functional SiO2@Au@SiO2@QD composite nanoparticles for integrated intracellular heating with temperature motoring. The particles are of multilayered concentric structure, consisting of Au nanoshells covered with quantum dots, with the former for infrared heating through localized surface plasma resonance while the later for temperature monitoring. The key to integrate plasmonic-heating/thermal-monitoring on a single composite nanoparticle is to ensure that the quantum dots be separated at a certain distance away from the Au shell surface in order to ensure a detectable quantum yield. Direct attachment of the quantum dots onto the Au shell would render the quantum dots practically functionless for temperature monitoring. To integrate quantum dots into Au nanoshells, a quantum quenching barrier of SiO2 was created by modifying a Stöber-like process. Materials, optical and thermal characterization was made of these composite nanoparticles. Cellular uptake of the nanoparticles was discussed. Experiments were performed on simultaneous in vitro heating and temperature monitoring in a cell internalized with the dual-functional SiO2@Au@SiO2@QD composite nanoparticles.
ABSTRACT
It was highlighted that the original article [1] contained an error in the Acknowledgments section.
ABSTRACT
BACKGROUND: Human brain models and pharmacological models of brain diseases are in high demand for drug screening because animal models have been found to be less than ideal for fully representing the human brain and are likely to fail during drug screening and testing; therefore, the construction of brain-like tissues is necessary. Due to the complexity of cortical tissue, the in vitro construction of brain-like tissue models has been restricted to mostly two-dimensional (2D) models and, on a limited scale, three-dimensional (3D) models. METHODS: In this study, 3D tissue blocks encapsulating neurons and astrocytes were constructed and cultured in vitro to mimic the cortex of the brain and to investigate the effects of astrocytes on the growth of neurons in a 3D culture. RESULTS: The results indicated that such methodology can provide a 3D culture environment suitable for neurons and astrocytes to live and function. When both cells were evenly mixed and cultured in a 3D manner, the astrocytes, which showed better outgrowth and a higher proliferation rate, benefited more than the neurons. On the other hand, the neurons benefited, showing longer axons and a denser network of dendrites, when they were accompanied by astrocytes at a certain distance. CONCLUSION: In conclusion, astrocytes stimulated the outgrowth of neurons in a 3D culture environment in vitro. Regardless, the spatial relationship between both types of cells should be controlled. Thus, culturing cells in a 3D manner is necessary to investigate the correlations between them. This study provides a foundation for biofabricating 3D neurons' cultures to allow for a deeper insight into the relationship between astrocytes or other glial cells and neurons in a 3D culture that is similar to the natural environment of the brain.
Subject(s)
Astrocytes/cytology , Cell Culture Techniques , Neuronal Outgrowth , Animals , Dendrites/metabolism , Mice , RatsABSTRACT
The purpose of this work is to find a method to locate the scattering centers in spatial domain; by using this information, the mean scatter spacing (MSS) can be estimated, and the spatial information is the one-dimensional imaging of scattering centers. This paper presents a method that can locate the scattering centers in spatial domain robustly and automatically. By incorporating it with fast Fourier transformation, the MSS can be estimated. The three foremost processes, matched filtering, envelope extraction, and peak reconstruction, are incorporated in the authors' algorithm. Monte Carlo simulations demonstrate that the proposed method is a robust one to locate scattering centers in spatial domain, and has a better performance than spectrum-based MSS estimation techniques. Especially exploited in estimating MSS which varies from 0.6 to 1.2 mm in the range of human mean trabecular bone spacing, the proposed method shows great potential in medical use. Simple but widely used phantom experiments demonstrate that the proposed algorithm has the capacity to locate scattering centers in spatial domain.
Subject(s)
Models, Theoretical , Sound Localization , Ultrasonic Waves , Bone Conduction , Cancellous Bone/physiology , Fourier Analysis , Humans , Signal-To-Noise RatioABSTRACT
PURPOSE: Dendritic cell-associated C-type lectin-1 (Dectin-1) and dendritic cell-specific intercellular adhesion molecule-3-grabbing non-integrin (DC-SIGN) play a crucial role in the early procedure of fungal pathogen defenses. The present study evaluated the associations between Dectin-1 and DC-SIGN gene single nucleotide polymorphisms (SNPs) and susceptibility to fungal keratitis (FK) in the northern Han Chinese population. METHODS: The polymorphisms of Dectin-1 (rs17206002, rs3901533, rs11053613, and rs3901532) and DC-SIGN (rs4804803, rs2287886, rs735239, and rs735240) for 109 FK patients and 220 matched healthy controls were determined by PCR and DNA direct sequencing assay. RESULTS: Each SNP was consistent with Hardy-Weinberg equilibrium (p>0.05). The frequencies of genotypes and alleles for rs735239 and rs735240 (DC-SIGN) showed statistical differences between patients and control groups (p<0.05). The wild G allele of rs735239 and the wild A allele of rs735240 were significantly higher in patients (p=0.003, OR=1.766, 95% confidence interval [CI] 1.207-2.585; p=0.014, OR=1.609, 95% CI 1.100-2.355, respectively). No association with a risk of FK was found for the remaining SNPs (p>0.05) even after ruling out clinical characteristics, such as severity degree and case history. Carriers of the haplotype TC (rs4804803 and rs2287886) had a higher risk of developing fungal keratitis (p=0.007, OR=1.710, 95% CI 1.154-2.534). The distribution of haplotypes AG and GA (rs735239 and rs735240) between the two groups also showed significant differences (p=0.014, p=0.003, respectively). CONCLUSIONS: Two SNPs of DC-SIGN (rs735239 and rs735240) are associated with susceptibility to FK in the northern Han Chinese population. The haplotypes of DC-SIGN may be susceptible to the risk of FK, whereas the analysis of Dectin-1 gene polymorphisms showed no significant association with FK risk. Further research with a larger sample is recommended.
Subject(s)
Aspergillosis/genetics , Cell Adhesion Molecules/genetics , Genetic Predisposition to Disease , Keratitis/genetics , Lectins, C-Type/genetics , Polymorphism, Single Nucleotide , Receptors, Cell Surface/genetics , Adult , Aged , Alleles , Asian People , Aspergillosis/ethnology , Aspergillosis/immunology , Aspergillosis/microbiology , Aspergillus fumigatus/immunology , Case-Control Studies , Cell Adhesion Molecules/immunology , Female , Gene Expression , Gene Frequency , Haplotypes , Heterozygote , Host-Pathogen Interactions , Humans , Keratitis/ethnology , Keratitis/immunology , Keratitis/microbiology , Lectins, C-Type/immunology , Male , Middle Aged , Receptors, Cell Surface/immunologyABSTRACT
Identifying differences between normal and tumor samples from a modular perspective may help to improve our understanding of the mechanisms responsible for colon cancer. Many cancer studies have shown that signaling transduction and biological pathways are disturbed in disease states, and expression profiles can distinguish variations in diseases. In this study, we integrated a weighted human signaling network and gene expression profiles to select risk modules associated with tumor conditions. Risk modules as classification features by our method had a better classification performance than other methods, and one risk module for colon cancer had a good classification performance for distinguishing between normal/tumor samples and between tumor stages. All genes in the module were annotated to the biological process of positive regulation of cell proliferation, and were highly associated with colon cancer. These results suggested that these genes might be the potential risk genes for colon cancer.
Subject(s)
Algorithms , Colonic Neoplasms/genetics , Gene Regulatory Networks , Genomics/methods , Signal Transduction , Classification/methods , Gene Expression Profiling , Genome, Human , HumansABSTRACT
Tendon defect repair remains a tough clinical procedure that hinders functional motion in patients. Electrohydrodynamic (EHD) three-dimensional (3D) printing, as a novel strategy, can controllably fabricate biomimetic micro/nanoscale architecture, but the hydrophobic and bioinert nature of polymers might be adverse to cell-material interplay. In this work, 3D EHD printed polycaprolactone (PCL) was immobilized on basic fibroblast growth factor (bFGF) using polydopamine (PDA), and the proliferation and tenogenic differentiation of tendon stem/progenitor cells (TSPCs) in vitro was researched. A subcutaneous model was established to evaluate the effects of tenogenesis and immunomodulation. We then investigated the in situ implantation and immunomodulation effects in an Achilles tendon defect model. After immobilization of bFGF, the scaffolds profoundly facilitated proliferation and tenogenic differentiation; however, PDA had only a proliferative effect. Intriguingly, the bFGF immobilized on EHD printed PCL indicated a synergistic effect on the highest expression of tenogenic gene and protein markers at 14 days, and the tenogenesis may be induced by activating the transforming growth factor-ß (TGF-ß) signal pathway in vitro. The subcutaneous engraftment study confirmed a tendon-like structure, similar to that of the native tendon, as well as an M2 macrophage polarization effect. Additionally, the bioactive scaffold exhibited superior efficacy in new collagen formation and repair of Achilles tendon defects. Our study revealed that the topographic cues alone were insufficient to trigger tenogenic differentiation, requiring appropriate chemical signals, and that appropriate immunomodulation was conducive to tenogenesis. The tenogenesis of TSPCs on the bioactive scaffold may be correlated with the TGF-ß signal pathway and M2 macrophage polarization.
Subject(s)
Achilles Tendon , Stem Cells , Humans , Cell Differentiation , Signal Transduction , Transforming Growth Factor beta/pharmacology , Tissue Engineering/methodsABSTRACT
Multiple infections are a key component of HPV pathogenesis and have a direct impact on how an infection turns out. It's crucial to look at the associations between HPV multiple infections and both age and HPV genotypes in the Chinese population, searching for the causative factors of multiple infections with a view to providing new ideas for the treatment and prevention of multiple infections. In this study, we retrospectively analyzed the data of HPV infections among outpatients from the 2019 year to the 2021 year of Shandong Maternal and Child Health Hospital. Analyzed the correlation between HPV multiple infections and age using logistic regression. Differences in the percentage of multiple infections between age groups were compared using the chi-square test. The chi-square test compared the differences in the distribution of 15 common HPV genotypes in mono- versus multiple infections. A two-dimensional matrix presented the frequency of HPV genotype combinations. Logistics regression analysis showed that age was significantly associated with the occurrence of multiple infections, with a dominance ratio OR 1.026 (95% CI 1.02-1.04). Interestingly, the proportion of HPV multiple infections among HPV-positive individuals increases with age in people older than 30 years of age. The chi-square test showed there was a difference in the distribution of HPV genotypes between multiple infections and mono- HPV infection (χ2 = 76.4; p = 0.000), a difference in the composition of HPV genotypes for dual versus single infections (χ2 = 90.6; p = 0.000) and a difference in HPV genotypes for triple versus single infections (χ2 = 56.7; p = 0.000). A 2 × 2 matrix showed that the combination of HPV52/HPV58 (30; 6.4%) was the combination of the highest frequency of infection for dual infections; The HPV52/HPV58 (21; 4.8%) combination was the highest frequency of HPV triple infection combination. HPV multiple infections were positively correlated with age; increasing age was positively correlated with the proportion of HPV multiple infections in the total infected population; the distribution of the 15 common genotypes of HPV differed between multiple infections and single infections; and HPV52:58 was a common type of infection combination in the Shandong population.
Subject(s)
Alphapapillomavirus , Human Papillomavirus Viruses , Papillomavirus Infections , Uterine Cervical Neoplasms , Female , Child , Humans , Adult , Retrospective Studies , Prevalence , Papillomaviridae/genetics , Genotype , China/epidemiologyABSTRACT
Carbon dots (CDs), a type of nanoparticle with excellent optical properties, good biocompatibility, and small size, are finding increasing application across the fields of biology and biomedicine. In recent years, biomass-derived CDs with pharmacological activity (BP-CDs) derived from herbal medicines (HMs), HMs extracts and other natural products with demonstrated pharmaceutical activity have attracted particular attention. Herein, we review recent advances in the development of BP-CDs, covering the selection of biomass precursors, different methods used for the synthesis of BP-CDs from natural sources, and the purification of BP-CDs. Additionally, we summarize the many remarkable properties of BP-CDs including optical properties, biocompatibility and pharmaceutical efficacy. Moreover, the antibacterial, antiviral, anticancer, biosensing, bioimaging, and other applications of BP-CDs are reviewed. Thereafter, we discuss the advantages and disadvantages of BP-CDs and Western drug-derived CDs, highlighting the excellent performance of BP-CDs. Finally, based on the current state of research on BP-CDs, we suggest several aspects of BP-CDs that urgently need to be addressed and identify directions that should be pursued in the future. This comprehensive review on BP-CDs is expected to guide the precise design, preparation, and future development of BP-CDs, thereby advancing the application of BP-CDs in biomedicine.