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1.
Nucleic Acids Res ; 52(12): 7063-7080, 2024 Jul 08.
Article in English | MEDLINE | ID: mdl-38808662

ABSTRACT

Cohesin plays a crucial role in the organization of topologically-associated domains (TADs), which influence gene expression and DNA replication timing. Whether epigenetic regulators may affect TADs via cohesin to mediate DNA replication remains elusive. Here, we discover that the histone demethylase PHF2 associates with RAD21, a core subunit of cohesin, to regulate DNA replication in mouse neural stem cells (NSC). PHF2 loss impairs DNA replication due to the activation of dormant replication origins in NSC. Notably, the PHF2/RAD21 co-bound genomic regions are characterized by CTCF enrichment and epigenomic features that resemble efficient, active replication origins, and can act as boundaries to separate adjacent domains. Accordingly, PHF2 loss weakens TADs and chromatin loops at the co-bound loci due to reduced RAD21 occupancy. The observed topological and DNA replication defects in PHF2 KO NSC support a cohesin-dependent mechanism. Furthermore, we demonstrate that the PHF2/RAD21 complex exerts little effect on gene regulation, and that PHF2's histone-demethylase activity is dispensable for normal DNA replication and proliferation of NSC. We propose that PHF2 may serve as a topological accessory to cohesin for cohesin localization to TADs and chromatin loops, where cohesin represses dormant replication origins directly or indirectly, to sustain DNA replication in NSC.


Subject(s)
Cell Cycle Proteins , Chromosomal Proteins, Non-Histone , Cohesins , DNA Replication , DNA-Binding Proteins , Neural Stem Cells , Animals , Cell Cycle Proteins/metabolism , Cell Cycle Proteins/genetics , Chromosomal Proteins, Non-Histone/metabolism , Chromosomal Proteins, Non-Histone/genetics , Neural Stem Cells/metabolism , Neural Stem Cells/cytology , Mice , DNA-Binding Proteins/metabolism , DNA-Binding Proteins/genetics , Chromatin/metabolism , Replication Origin , Histone Demethylases/metabolism , Histone Demethylases/genetics , Nuclear Proteins/metabolism , Nuclear Proteins/genetics , Genome/genetics , CCCTC-Binding Factor/metabolism , CCCTC-Binding Factor/genetics , Mice, Knockout
2.
Immunol Rev ; 308(1): 168-186, 2022 07.
Article in English | MEDLINE | ID: mdl-35582842

ABSTRACT

Maternal tolerance to semi- or fully allograft conceptus is a prerequisite for the maintenance of pregnancy. Once this homeostasis is disrupted, it may result in pregnancy loss. As a potential approach to prevent pregnancy loss, targeting decidual immune cells (DICs) at the maternal-fetal interface has been suggested. Although the phenotypic features and functions of DIC have been extensively profiled, the regulatory pathways for this unique immunological adaption have yet to be elucidated. In recent years, a pivotal mechanism has been highlighted in the area of immunometabolism, by which the changes in intracellular metabolic pathways in DIC and interaction with the adjacent metabolites in the microenvironment can alter their phenotypes and function. More inspiringly, the manipulation of metabolic profiling in DIC provides a novel avenue for the prevention and treatment of pregnancy loss. Herein, this review highlights the major metabolic programs (specifically, glycolysis, ATP-adenosine metabolism, lysophosphatidic acid metabolism, and amino acid metabolism) in multiple immune cells (including decidual NK cells, macrophages, and T cells) and their integrations with the metabolic microenvironment in normal pregnancy. Importantly, this perspective may help to provide a potential therapeutic strategy for reducing pregnancy loss via targeting this interplay.


Subject(s)
Decidua , Killer Cells, Natural , Female , Humans , Immune Tolerance , Macrophages , Pregnancy , T-Lymphocytes
3.
PLoS Pathog ; 19(12): e1011576, 2023 Dec.
Article in English | MEDLINE | ID: mdl-38109366

ABSTRACT

Mucosal immunity is critical to host protection from enteric pathogens and must be carefully controlled to prevent immunopathology. Regulation of immune responses can occur through a diverse range of mechanisms including bi-directional communication with neurons. Among which include specialized sensory neurons that detect noxious stimuli due to the expression of transient receptor potential vanilloid receptor 1 (TRPV1) ion channel and have a significant role in the coordination of host-protective responses to enteric bacterial pathogens. Here we have used the mouse-adapted attaching and effacing pathogen Citrobacter rodentium to assess the specific role of TRPV1 in coordinating the host response. TRPV1 knockout (TRPV1-/-) mice had a significantly higher C. rodentium burden in the distal colon and fecal pellets compared to wild-type (WT) mice. Increased bacterial burden was correlated with significantly increased colonic crypt hyperplasia and proliferating intestinal epithelial cells in TRPV1-/- mice compared to WT. Despite the increased C. rodentium burden and histopathology, the recruitment of colonic T cells producing IFNγ, IL-17, or IL-22 was similar between TRPV1-/- and WT mice. In evaluating the innate immune response, we identified that colonic neutrophil recruitment in C. rodentium infected TRPV1-/- mice was significantly reduced compared to WT mice; however, this was independent of neutrophil development and maturation within the bone marrow compartment. TRPV1-/- mice were found to have significantly decreased expression of the neutrophil-specific chemokine Cxcl6 and the adhesion molecules Icam1 in the distal colon compared to WT mice. Corroborating these findings, a significant reduction in ICAM-1 and VCAM-1, but not MAdCAM-1 protein on the surface of colonic blood endothelial cells from C. rodentium infected TRPV1-/- mice compared to WT was observed. These findings demonstrate the critical role of TRPV1 in regulating the host protective responses to enteric bacterial pathogens, and mucosal immune responses.


Subject(s)
Enterobacteriaceae Infections , Intestinal Mucosa , Mice , Animals , Intestinal Mucosa/metabolism , Colon/pathology , Citrobacter rodentium , Endothelial Cells/metabolism , Immunity, Innate , Mice, Inbred C57BL , Mice, Knockout , TRPV Cation Channels/genetics , TRPV Cation Channels/metabolism
4.
J Immunol ; 210(11): 1771-1789, 2023 06 01.
Article in English | MEDLINE | ID: mdl-37017564

ABSTRACT

The type IV IFN (IFN-υ) is reported in vertebrates from fish to primary mammals with IFN-υR1 and IL-10R2 as receptor subunits. In this study, the proximal promoter of IFN-υ was identified in the amphibian model, Xenopus laevis, with functional IFN-sensitive responsive element and NF-κB sites, which can be transcriptionally activated by transcription factors, such as IFN regulatory factor (IRF)1, IRF3, IRF7, and p65. It was further found that IFN-υ signals through the classical IFN-stimulated gene (ISG) factor 3 (ISGF3) to induce the expression of ISGs. It seems likely that the promoter elements of the IFN-υ gene in amphibians is similar to type III IFN genes, and that the mechanism involved in IFN-υ induction is very much similar to type I and III IFNs. Using recombinant IFN-υ protein and the X. laevis A6 cell line, >400 ISGs were identified in the transcriptome, including ISGs homologous to humans. However, as many as 268 genes were unrelated to human or zebrafish ISGs, and some of these ISGs were expanded families such as the amphibian novel TRIM protein (AMNTR) family. AMNTR50, a member in the family, was found to be induced by type I, III, and IV IFNs through IFN-sensitive responsive element sites of the proximal promoter, and this molecule has a negative role in regulating the expression of type I, III, and IV IFNs. It is considered that the current study contributes to the understanding of transcription, signaling, and functional aspects of type IV IFN at least in amphibians.


Subject(s)
Interferon Type I , Interferons , Animals , Humans , Xenopus laevis , Interferons/genetics , Interferons/metabolism , Zebrafish/metabolism , Gene Expression Regulation , Signal Transduction , Interferon Type I/metabolism , Mammals/metabolism
5.
J Proteome Res ; 23(4): 1272-1284, 2024 04 05.
Article in English | MEDLINE | ID: mdl-38470452

ABSTRACT

Gestational diabetes mellitus (GDM) with intrauterine hyperglycemia induces a series of changes in the placenta, which have adverse effects on both the mother and the fetus. The aim of this study was to investigate the changes in the placenta in GDM and its gender differences. In this study, we established an intrauterine hyperglycemia model using ICR mice. We collected placental specimens from mice before birth for histological observation, along with tandem mass tag (TMT)-labeled proteomic analysis, which was stratified by sex. When the analysis was not segregated by sex, the GDM group showed 208 upregulated and 225 downregulated proteins in the placenta, primarily within the extracellular matrix and mitochondria. Altered biological processes included cholesterol metabolism and oxidative stress responses. After stratification by sex, the male subgroup showed a heightened tendency for immune-related pathway alterations, whereas the female subgroup manifested changes in branched-chain amino acid metabolism. Our study suggests that the observed sex differences in placental protein expression may explain the differential impact of GDM on offspring.


Subject(s)
Diabetes, Gestational , Hyperglycemia , Humans , Pregnancy , Female , Male , Mice , Animals , Placenta/metabolism , Proteomics , Mice, Inbred ICR , Diabetes, Gestational/genetics , Diabetes, Gestational/metabolism , Hyperglycemia/genetics
6.
PLoS Pathog ; 18(1): e1010204, 2022 01.
Article in English | MEDLINE | ID: mdl-35030230

ABSTRACT

The hepatitis B virus (HBV) core protein (HBc) functions in multiple steps of the viral life cycle. Heteroaryldihydropyrimidine compounds (HAPs) such as Bay41-4109 are capsid protein allosteric modulators that accelerate HBc degradation and inhibit the virion secretion of HBV, specifically by misleading HBc assembly into aberrant non-capsid polymers. However, the subsequent cellular fates of these HAP-induced aberrant non-capsid polymers are not well understood. Here, we discovered that that the chaperone-binding E3 ubiquitin ligase protein STUB1 is required for the removal of Bay41-4109-induced aberrant non-capsid polymers from HepAD38 cells. Specifically, STUB1 recruits BAG3 to transport Bay41-4109-induced aberrant non-capsid polymers to the perinuclear region of cells, thereby initiating p62-mediated macroautophagy and lysosomal degradation. We also demonstrate that elevating the STUB1 level enhances the inhibitory effect of Bay41-4109 on the production of HBeAg and HBV virions in HepAD38 cells, in HBV-infected HepG2-NTCP cells, and in HBV transgenic mice. STUB1 overexpression also facilitates the inhibition of Bay41-4109 on the cccDNA formation in de novo infection of HBV. Understanding these molecular details paves the way for applying HAPs as a potentially curative regimen (or a component of a combination treatment) for eradicating HBV from hepatocytes of chronic infection patients.


Subject(s)
Antiviral Agents/pharmacology , Capsid Proteins/drug effects , Hepatitis B virus/drug effects , Hepatitis B virus/metabolism , Ubiquitin-Protein Ligases/metabolism , Animals , Capsid Proteins/metabolism , Hepatitis B/virology , Humans , Macroautophagy/drug effects , Mice
7.
Inorg Chem ; 2024 Sep 20.
Article in English | MEDLINE | ID: mdl-39303061

ABSTRACT

Zero-dimensional (0D) hybrid organic-inorganic bismuth halides have attracted immense scientific interest as promising candidates for lead-free materials. Here, by using a typical solvothermal method, two mixed-cation-phase 0D hybrid bismuth chlorides of [HPDA][H2PDA]BiCl6 (1) and [Hbzim][H2PA]BiCl6 (2) (PDA = bis(4-pyridyl)amine, bzim = benzimidazole, PA = 2-picolylamine) have been assembled based on a series of organic amine guests. Both compounds exhibit interesting photoluminescence phenomena, in which compound 1 exhibits a double emission property of blue fluorescence and yellow-green phosphorescence simultaneously, while compound 2 exhibits wide-band yellow-green emission under visible light excitation. The luminescence mechanism is explained by experiments and theoretical calculations. In view of the fact that halometallate units and the conjugated nitrogen heterocyclic systems can act as electron donors and electron acceptors, respectively, both compounds exhibit free radical-driven photochromism induced by electron transfer under xenon lamp irradiation at room temperature. In addition, benefiting from abundant hydrogen bond networks in structures, the two compounds show significant temperature-dependent proton conduction behavior in the range of 298-343 K, and the proton conductivity of both compounds is significantly improved after light irradiation. Our study demonstrates two novel hybrid mixed-cation-phase 0D hybrid bismuth halides with photoluminescence, photochromism, and photomodulated proton conduction properties, which enriches the dual-template-directed metal halide system and provides a feasible scheme for the synthesis of photoresponsive smart materials.

8.
Fish Shellfish Immunol ; 150: 109662, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38821229

ABSTRACT

SIRT6, a key member of the sirtuin family, plays a pivotal role in regulating a number of vital biological processes, including energy metabolism, oxidative stress, and immune system modulation. Nevertheless, the function of SIRT6 in bony fish, particularly in the context of antiviral immune response, remains largely unexplored. In this study, a sirt6 was cloned and characterized in a commercial fish, the Chinese perch (Siniperca chuatsi). The SIRT6 possesses conserved SIR2 domain with catalytic core region when compared with other vertebrates. Tissue distribution analysis indicated that sirt6 was expressed in all detected tissues, and the sirt6 was significantly induced following infection of infectious haemorrhagic syndrome virus (IHSV). The overexpression of SIRT6 resulted in significant upregulation of interferon-stimulated genes (ISGs), such as viperin, mx, isg15, irf3 and ifp35, and inhibited viral replication. It was further found that SIRT6 was located in nucleus and could enhance the expression of ISGs induced by type I and II IFNs. These findings may provide new information in relation with the function of SIRT6 in vertebrates, and with viral prevention strategy development in aquaculture.


Subject(s)
Amino Acid Sequence , Fish Diseases , Fish Proteins , Gene Expression Regulation , Immunity, Innate , Perches , Phylogeny , Rhabdoviridae Infections , Sirtuins , Animals , Sirtuins/genetics , Sirtuins/immunology , Sirtuins/metabolism , Fish Diseases/immunology , Fish Diseases/virology , Fish Proteins/genetics , Fish Proteins/immunology , Fish Proteins/chemistry , Immunity, Innate/genetics , Rhabdoviridae Infections/immunology , Rhabdoviridae Infections/veterinary , Gene Expression Regulation/immunology , Perches/immunology , Sequence Alignment/veterinary , Gene Expression Profiling/veterinary
9.
BMC Infect Dis ; 24(1): 578, 2024 Jun 11.
Article in English | MEDLINE | ID: mdl-38862881

ABSTRACT

BACKGROUND: Tuberculosis (TB) remains a global public health event of great concern, however epidemic data on TB covering entire areas during the special period of the COVID-19 epidemic have rarely been reported. We compared the dissemination and multidrug-resistance patterns of Mycobacterium tuberculosis complex (MTBC) in the main urban area of Luoyang City, China (including six municipal jurisdictions) and nine county and township areas under its jurisdiction, aimed to establish the epidemiology of TB in this region and to provide reference for precision anti-TB in places with similar settings. METHODS: From 2020 to 2022, sputum samples were collected from 18,504 patients with confirmed, suspected and unexcluded TB in 10 designated TB medical institutions. Insertion sequence 6110 was amplified by PCR (rpoB gene detection if necessary) to confirm the presence of MTBC. PCR-positive specimens were analyzed by multicolor melting curve analysis to detect multidrug resistance. RESULTS: Among the 18,504 specimens, 2675 (14.5%) were MTBC positive. The positive rate was higher in the main urban area than in the county and township areas (29.8% vs. 10.9%, p < 0.001). Male, re-treated and smear-positive groups were high-burden carriers of MTBC. Individuals aged > 60 years were the largest group infected with MTBC in the main urban area, compared with individuals aged < 61 years in the county and township areas. The detection of multidrug-resistant TB (MDR-TB) was higher in the main urban area than in the county and township areas (13.9% vs. 7.8%, p < 0.001). In all areas, MDR-TB groups were dominated by males, patients with a history of TB treatment, and patients aged < 61 years. Stratified analysis of MDR-TB epidemiology showed that MDR4 (INH þ RIF þ EMB þ SM) was predominant in the main urban area, while MDR3 (INH þ RIF þ SM) was predominant in the county and township areas. MDR-TB detection rate and epidemiology differed among the county and township areas. CONCLUSIONS: For local TB control, it is necessary to plan more appropriate and accurate prevention and control strategies according to the regional distribution of MTBC infection.


Subject(s)
COVID-19 , Mycobacterium tuberculosis , Tuberculosis, Multidrug-Resistant , Humans , Male , Middle Aged , Female , Mycobacterium tuberculosis/drug effects , Mycobacterium tuberculosis/genetics , Mycobacterium tuberculosis/isolation & purification , China/epidemiology , Adult , Tuberculosis, Multidrug-Resistant/epidemiology , Tuberculosis, Multidrug-Resistant/microbiology , Tuberculosis, Multidrug-Resistant/drug therapy , COVID-19/epidemiology , Aged , Adolescent , Young Adult , Drug Resistance, Multiple, Bacterial/genetics , Antitubercular Agents/pharmacology , Antitubercular Agents/therapeutic use , Child , Sputum/microbiology , SARS-CoV-2/genetics , SARS-CoV-2/drug effects , Child, Preschool , Aged, 80 and over , Infant , Epidemics
10.
BMC Cardiovasc Disord ; 24(1): 502, 2024 Sep 19.
Article in English | MEDLINE | ID: mdl-39300362

ABSTRACT

BACKGROUND: The post-processing technology of CTA offers significant advantages in evaluating left atrial enlargement (LAE) in patients with persistent atrial fibrillation (PAF). This study aims to identify parameters for rapidly and accurately diagnosing LAE in patients with PAF using CT cross-sections. METHODS: Left atrial pulmonary venous (PV) CT was performed to 300 PAF patients with dual-source CT, and left atrial volume (LAV), left atrial anteroposterior diameter (LAD1), left atrial transverse diameter (LAD2), and left atrial area (LAA) were measured in the ventricular end systolic (ES) and middle diastolic (MD). LA index (LAI) = LA parameter/body surface area (BSA). Left atrial volume index (LAVIES) > 77.7 ml/m2 was used as the reference standard for the LAE diagnosis. RESULTS: 227 patients were enrolled in the group, 101 (44.5%) of whom had LAE. LAVES and LAVMD (r = 0.983), LAVIES and LAVIMD (r = 0.984), LAAES and LAVIES (r = 0.817), LAAMD and LAVIES (r = 0.814) had strong positive correlations. The area under curve (AUC) showed that all measured parameters were suitable for diagnosing LAE, and the diagnostic efficacy was compared as follows: LAA/LAAI> LAD> the relative value index of LAD, LAD2> LAD1. LAA and LAAI demonstrated comparable diagnostic efficacy, with LAA being more readily available than LAAI. CONCLUSIONS: The axial LAA measured by CTA can be served as a parameter for the rapid and accurate diagnosis of LAE in patients with PAF.


Subject(s)
Atrial Fibrillation , Computed Tomography Angiography , Heart Atria , Predictive Value of Tests , Humans , Atrial Fibrillation/diagnostic imaging , Atrial Fibrillation/diagnosis , Atrial Fibrillation/physiopathology , Female , Male , Middle Aged , Heart Atria/diagnostic imaging , Heart Atria/physiopathology , Aged , Reproducibility of Results , Atrial Function, Left , Atrial Remodeling , Retrospective Studies , Cardiomegaly/diagnostic imaging , Multidetector Computed Tomography , Pulmonary Veins/diagnostic imaging , Pulmonary Veins/physiopathology
11.
Surg Endosc ; 38(2): 880-887, 2024 Feb.
Article in English | MEDLINE | ID: mdl-38082011

ABSTRACT

OBJECTIVE: This study aimed to evaluate the clinical application and efficacy of a super-low-positioned intestinal decompression tube in the treatment of intestinal obstruction. METHODS: A total of 130 patients with postoperative small bowel obstruction were included in this study. The patients were divided into a super-low-positioned intestinal decompression group and a conventional intestinal decompression group. The clinical data, treatment outcomes, and complications were compared between the two groups. RESULTS: The technical success rate of placing the super-low-positioned intestinal decompression tube was 100%, with no intraoperative complications. The patients in the super-low-positioned intestinal decompression group had a significantly shorter hospital stay (8.3 ± 5.2 vs 17.7 ± 13.3, P < 0.001) and a higher non-operative treatment success rate (83.6% vs 57.9%, P = 0.001) compared to the conventional intestinal decompression group. Multivariate logistic regression analysis showed that the placement of a super-low-positioned intestinal decompression tube was an independent protective factor for treatment outcomes (P = 0.001). The hospital stay was significantly shorter in the super-low-positioned intestinal decompression group compared to the conventional group in both successful non-operative treatment patients (6.9 ± 3.0 vs 11.2 ± 7.5, P < 0.001) and failed non-operative treatment patients (16.2 ± 7.4 vs 26.6 ± 14.4, P < 0.001). The super-low-positioned intestinal decompression tube effectively relieved the "Self-strangulation" phenomenon in patients with intestinal obstruction. CONCLUSION: The super-low-positioned intestinal decompression tube is a safe and effective method for the treatment of intestinal obstruction, with better treatment outcomes and shorter hospital stays compared to conventional intestinal decompression. Further prospective studies are needed to validate these findings.


Subject(s)
Intestinal Obstruction , Humans , Pilot Projects , Retrospective Studies , Intestinal Obstruction/etiology , Intestinal Obstruction/surgery , Treatment Outcome , Postoperative Complications/etiology , Decompression/adverse effects
12.
Cell Biochem Funct ; 42(3): e3996, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38561942

ABSTRACT

Breast cancer (BC) poses a persistent global health challenge, particularly in countries with elevated human development indices linked to factors such as increased life expectancy, education, and wealth. Despite therapeutic progress, challenges persist, and the role of epitranscriptomic RNA modifications in BC remains inadequately understood. The epitranscriptome, comprising diverse posttranscriptional modifications on RNA molecules, holds the potential to intricately modulate RNA function and regulation, implicating dysregulation in various diseases, including BC. Noncoding RNAs (ncRNAs), acting as posttranscriptional regulators, influence physiological and pathological processes, including cancer. RNA modifications in long noncoding RNAs (lncRNAs) and microRNAs (miRNAs) add an extra layer to gene expression control. This review delves into recent insights into epitranscriptomic RNA modifications, such as N-6-methyladenosine (m6A), adenine-to-inosine (A-to-I) editing, and 5-methylcytosine (m5C), specifically in the context of lncRNA and miRNAs in BC, highlighting their potential implications in BC development and progression. Understanding this intricate regulatory landscape is vital for deciphering the molecular mechanisms underlying BC and identifying potential therapeutic targets.


Subject(s)
Adenine/analogs & derivatives , Breast Neoplasms , MicroRNAs , RNA, Long Noncoding , Humans , Female , MicroRNAs/genetics , MicroRNAs/metabolism , RNA, Long Noncoding/genetics , RNA, Long Noncoding/metabolism , Breast Neoplasms/genetics , Breast Neoplasms/pathology
13.
BMC Pediatr ; 24(1): 455, 2024 Jul 16.
Article in English | MEDLINE | ID: mdl-39014321

ABSTRACT

The impact of the Coronavirus Disease 2019 (COVID-19) on society is continuous, resulting in negative psychological consequences. Given the vulnerability and sensitivity to the environment among preschool children, their emotional and behavioral problems deserve more attention. The current study aimed to explore the impact of the epidemic on preschool children's mental health by determining the pooled prevalence of emotional and behavioral problems amidst the Coronavirus Disease 2019 pandemic and to reveal potential reasons for variations between studies. Published studies were searched in Embase, PubMed, ProQuest, PsycINFO, Web of Science, CNKI, and Wanfang. Based on the inclusion criteria outlined in this study, a total of 10 studies encompassing 38,059 participants were incorporated. Employing a random-effect model for estimating the prevalence of emotional and behavioral problems, the results revealed a pooled prevalence rate of 24.3% (95% CI, 0.15-0.38; I²=99.9%) among preschool children. This rate surpasses the pre-outbreak prevalence observed in different countries, signifying a detrimental influence of the epidemic on the mental well-being of preschoolers. Therefore, mental health care and recovery are essential for the vulnerable group during and after the public health crisis. Specific emotional and behavioral problems among preschool children are expected to be researched in the future to provide more targeted guidance for intervention.


Subject(s)
COVID-19 , Humans , COVID-19/psychology , COVID-19/epidemiology , Child, Preschool , Child Behavior Disorders/epidemiology , Child Behavior Disorders/psychology , Prevalence , Problem Behavior/psychology , Affective Symptoms/epidemiology , Affective Symptoms/psychology , SARS-CoV-2
14.
BMC Musculoskelet Disord ; 25(1): 680, 2024 Aug 29.
Article in English | MEDLINE | ID: mdl-39210324

ABSTRACT

BACKGROUND: This study aimed to evaluate the causal relationship between Interleukin-27 (IL-27) and osteoporosis by bidirectional Mendelian randomization (MR) analysis. METHODS: Firstly, the genome-wide association study summary data of osteoporosis (finn-b-M13_OSTEOPOROSIS) and IL-27 levels (ebi-a-GCST90012017) were picked out from the Integrative Epidemiology Unit (IEU) OpenGWAS database. After filtrating instrumental variables (IVs), the bidirectional MR analysis between IL-27 levels and osteoporosis was performed by MR-Egger, Weighted median, Simple mode, Weighted mode, and Inverse variance weighted (IVW). Subsequently, the sensitivity analysis was adopted to evaluate the reliability of the MR results via the Heterogeneity, Horizontal pleiotropy test and Leave-One-Out (LOO) analysis. Finally, the enrichment analysis of genes corresponding to SNPs related to IL-27 levels derived from eQTLGen database was executed to explore in depth the biological function and regulatory mechanism of these genes on osteoporosis occurrence. RESULTS: The bidirectional MR results based on IVW method revealed that IL-27 level as a risk factor was causally related to osteoporosis (P = 0.004, odds ratio (OR) = 1.123, 95% confidence interval (CI) = 1.037-1.217), whereas osteoporosis was not in significant connection with IL-27 levels (P > 0.05). In regard to the sensitivity analysis for forward MR results, there was no heterogeneity and horizontal pleiotropy, and no SNPs relevant to IL-27 levels existed severe bias, suggesting the reliability of forward MR analysis. Furthermore, a total of 74 genes corresponding to 26 SNPs of IL-27 levels were obtained and were mainly involved in immune and inflammatory pathways including MyD88-dependent toll-like receptor signaling pathway, Toll-like receptor signaling pathway, cytosolic DNA-sensing pathway and so forth. CONCLUSIONS: This study supported that IL-27 level as a risk factor was causally connected with osteoporosis and might regulate the disease occurrence and progression by means of immune and inflammatory mechanisms, which could provide important reference and evidence for further exploring the role of IL-27 in the development of osteoporosis.


Subject(s)
Genome-Wide Association Study , Mendelian Randomization Analysis , Osteoporosis , Polymorphism, Single Nucleotide , Humans , Osteoporosis/genetics , Osteoporosis/epidemiology , Interleukins/genetics , Risk Factors , Genetic Predisposition to Disease , Interleukin-27/genetics , Databases, Genetic
15.
BMC Genomics ; 24(1): 619, 2023 Oct 18.
Article in English | MEDLINE | ID: mdl-37853311

ABSTRACT

To explore the potential network markers and related signaling pathways of human B cells infected by COVID-19, we performed standardized integration and analysis of single-cell sequencing data to construct conditional cell-specific networks (CCSN) for each cell. Then the peripheral blood cells were clustered and annotated based on the conditional network degree matrix (CNDM) and gene expression matrix (GEM), respectively, and B cells were selected for further analysis. Besides, based on the CNDM of B cells, the hub genes and 'dark' genes (a gene has a significant difference between case and control samples not in a gene expression level but in a conditional network degree level) closely related to COVID-19 were revealed. Interestingly, some of the 'dark' genes and differential degree genes (DDGs) encoded key proteins in the JAK-STAT pathway, which had antiviral effects. The protein p21 encoded by the 'dark' gene CDKN1A was a key regulator for the COVID-19 infection-related signaling pathway. Elevated levels of proteins encoded by some DDGs were directly related to disease severity of patients with COVID-19. In short, the proteins encoded by 'dark' genes complement some missing links in COVID-19 and these signaling pathways played an important role in the growth and activation of B cells.


Subject(s)
COVID-19 , Signal Transduction , Humans , Signal Transduction/genetics , Janus Kinases/genetics , STAT Transcription Factors/genetics , COVID-19/genetics , Gene Regulatory Networks , Gene Expression Profiling
16.
Am J Physiol Lung Cell Mol Physiol ; 324(1): L53-L63, 2023 01 01.
Article in English | MEDLINE | ID: mdl-36410021

ABSTRACT

It is becoming increasingly appreciated that the nervous and immune systems communicate bidirectionally to regulate immunological outcomes in a variety of organs including the lung. Activation of neuronal signaling can be induced by inflammation, tissue damage, or pathogens to evoke or reduce immune cell activation in what has been termed a neuroimmune reflex. In the periphery, these reflexes include the cholinergic anti-inflammatory pathway, sympathetic reflex, and sensory nociceptor-immune cell pathways. Continual advances in neuroimmunology in peripheral organ systems have fueled small-scale clinical trials that have yielded encouraging results for a range of immunopathologies such as rheumatoid arthritis. Despite these successes, several limitations should give clinical investigators pause in the application of neural stimulation as a therapeutic for lung inflammation, especially if inflammation arises from a novel pathogen. In this review, the general mechanisms of each reflex, the evidence for these circuits in the control of lung inflammation, and the key knowledge gaps in our understanding of these neuroimmune circuits will be discussed. These limitations can be overcome not only through a better understanding of neuroanatomy but also through a systematic evaluation of stimulation parameters using immune activation in lung tissues as primary readouts. Our rapidly evolving understanding of the nervous and immune systems highlights the importance of communication between these cells in health and disease. This integrative approach has tremendous potential in the development of targeted therapeutics if specific challenges can be overcome.


Subject(s)
Arthritis, Rheumatoid , Pneumonia , Humans , Inflammation/metabolism
17.
Reproduction ; 165(5): 543-555, 2023 05 01.
Article in English | MEDLINE | ID: mdl-36809184

ABSTRACT

In brief: Hypoxia is vital for the establishment of the maternal-fetal interface during early pregnancy. This study shows that decidual macrophages (dMφ) could be recruited and reside in decidua under the regulation of hypoxia/VEGFA-CCL2 axis. Abstract: Infiltration and residence of decidual macrophages (dMφ) are of great significance to pregnancy maintenance for their role in angiogenesis, placental development, and inducing immune tolerance. Besides, hypoxia has now been acknowledged as an important biological event at maternal-fetal interface in the first trimester. However, whether and how hypoxia regulates biofunctions of dMφ remain elusive. Herein, we observed increased expression of C-C motif chemokine ligand 2 (CCL2) and residence of macrophages in decidua compared to secretory-phase endometrium. Moreover, hypoxia treatment on stromal cells improved the migration and adhesion of dMφ. Mechanistically, these effects might be mediated by upregulated CCL2 and adhesion molecules (especially ICAM2 and ICAM5) on stromal cells in the presence of endogenous vascular endothelial growth factor-A (VEGFA) in hypoxia. These findings were also verified by recombinant VEGFA and indirect coculture, indicating that the interaction between stromal cells and dMφ in hypoxia condition may facilitate dMφ recruitment and residence. In conclusion, VEGFA derived from a hypoxic environment may manipulate CCL2/CCR2 and adhesion molecules to enhance the interactions between dMφ and stromal cells and thus contribute to the enrichment of macrophages in decidua early during normal pregnancy.


Subject(s)
Decidua , Placenta , Pregnancy , Female , Humans , Placenta/metabolism , Decidua/metabolism , Vascular Endothelial Growth Factor A/metabolism , Chemotaxis , Ligands , Macrophages/metabolism , Chemokines/metabolism , Chemokine CCL2/metabolism
18.
Macromol Rapid Commun ; 44(23): e2300379, 2023 Dec.
Article in English | MEDLINE | ID: mdl-37673414

ABSTRACT

Keratitis caused by drug-resistant bacteria is a severe condition that can lead to corneal perforation and even blindness, making effective treatment a top priority amid growing antibiotic resistance. Eye drops for anti-inflammatory treatment necessitate frequent administration of high doses throughout every day due to bacterial resistance resulting from antibiotic overuse and the low bioavailability of drugs. To overcome these issues, an antibacterial nanocomposite is prepared via conjugating random copolymers of galactose and 3-(acrylamide)phenylboronic acid to the surface of silver nanoparticles. The customized nanocomposites trigger specific binding to bacteria, resulting in excellent retention of the drug on the ocular surface, resulting in rapid and powerful killing of bacteria and inhibition of bacterial proliferation. Due to its superior drug delivery capabilities to the ocular surface, the functionalized nanocomplex markedly amplifies the anti-inflammatory efficacy, even at low doses. This effect is achieved by impeding immune cell infiltration and diminishing the synthesis of inflammatory mediators and cytokines, thereby suggesting enhanced healing properties for corneal inflammation. This study demonstrates a promising nanocomposite which is an effective and safe antibacterial strategy for bacterial keratitis with favorable prognostic and clinical conversion potential.


Subject(s)
Keratitis , Metal Nanoparticles , Humans , Silver/pharmacology , Silver/chemistry , Pharmaceutical Preparations , Metal Nanoparticles/therapeutic use , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/therapeutic use , Anti-Bacterial Agents/chemistry , Keratitis/drug therapy , Keratitis/microbiology , Bacteria , Anti-Inflammatory Agents/pharmacology , Anti-Inflammatory Agents/therapeutic use
19.
Environ Res ; 239(Pt 1): 117358, 2023 Dec 15.
Article in English | MEDLINE | ID: mdl-37821070

ABSTRACT

Here, we have demonstrated an innovative decontamination strategy using molten salts as a solvent to clean stubborn uranium contaminants on stainless steel surfaces. The aim of this work was to investigate the evolutionary path of contaminants in molten salts to reveal the decontamination mechanism, thus providing a basis for the practical application of the method. Thermodynamic analysis revealed that alkali metal hydroxides, carbonates, chlorides and nitrates can react with uranium oxides (UO3 and U3O8) to form various uranates. Notably, the decontamination mechanism was elucidated by analyzing the chemical composition of the contaminants in the molten salts and the surface morphology of the specimens considering NaOH-Na2CO3-NaCl melt as the decontaminant. The decontamination process involved two stages: a rapid decontamination stage dominated by the thermal effect of molten salt, and a stable decontamination stage governed by the chemical reactions and diffusion of molten salt. Subsequently, a multiple decontamination strategy was implemented to achieve high decontamination rates and low residual radioactivity. Within the actual cleaning time of 30 min, the decontamination efficiency (DE) of UO3-contaminated specimens reached 97.8% and 93.0% for U3O8-contaminated specimens. Simultaneously, the radioactivity levels of all specimens were reduced to below the control level for reuse in the nuclear domain. Particularly, the actual radioactive waste from the nuclear industry reached a reusable level of radioactivity after decontamination. The NaOH-Na2CO3-NaCl melt outperforms conventional chemical solvents and may be one of the most rapid and efficient decontaminants for stubborn uranium contamination of metal surfaces, which provides insights in regard to handling nuclear waste.


Subject(s)
Radioactivity , Uranium , Sodium Chloride , Stainless Steel , Salts , Sodium Hydroxide , Solvents
20.
Environ Res ; 231(Pt 1): 116042, 2023 Aug 15.
Article in English | MEDLINE | ID: mdl-37142084

ABSTRACT

Bio-electrochemical systems (BESs) have attracted wide attention in the field of wastewater treatment owing to their fast electron transfer rate and high performance. Unfortunately, the low electro-chemical activity of carbonaceous materials commonly used in BESs remains a bottleneck for their practical applications. Especially, for refractory pollutants remediation, the efficiency is largely limited by the cathode property in term of (bio)-electrochemical reduction of highly oxidized functional groups. Herein, a reduced graphene oxide (rGO) and polyaniline (PANI) modified electrode was fabricated via two-step electro-deposition using carbon brush as raw material. Benefiting from the modified graphene sheets and PANI nanoparticles, the rGO/PANI electrode shows highly conductive network with the electro-active surface area increased by 12 times (0.013 mF cm-2) and the charge transfer resistance decreased by 92% (0.23Ω) comparing with the unmodified one. Most importantly, the rGO/PANI electrode used as abiotic cathode achieves highly efficient azo dye removal from wastewater. The highest decolorization efficiency reaches 96 ± 0.03% within 24 h and the maximum decolorization rate is as high as 20.9 ± 1.45 g h-1·m-3. The features of improved electro-chemical activity and enhanced pollutant removal efficiency provide a new insight toward development of high performance BESs via electrode modification for practical application.


Subject(s)
Graphite , Graphite/chemistry , Azo Compounds , Electrodes
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