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Experimental and Therapeutic Medicine Aug 2024Inflammation serves as a multifaceted defense mechanism activated by pathogens, cellular damage and irritants, aiming to eliminate primary causes of injury and promote...
Inflammation serves as a multifaceted defense mechanism activated by pathogens, cellular damage and irritants, aiming to eliminate primary causes of injury and promote tissue repair. Miq (), prevalent in Vietnam and southern China, has a history of traditional use for treating cough, fever and asthma. Previous studies on its phytochemicals have shown their potential as anti-inflammatory agents, yet underlying mechanisms remain to be elucidated. The present study investigated the regulatory effects of on the anti-inflammatory pathways. The methanol extracts of (PDME) were found to inhibit nitric oxide (NO) production and induce heme oxygenase-1 (HO-1) expression in murine macrophages. While MAPKs inhibitors, such as SP600125, SB203580 and U0126 did not regulate HO-1 expression, the treatment of cycloheximide, a translation inhibitor, reduced HO-1. Furthermore, PDME inhibited lipopolysaccharide (LPS)-induced inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2) and TNF-α expression at both the mRNA and protein levels. The activity of NOS and the expression of TNF-α, iNOS and COX-2 decreased in LPS-stimulated Raw 264.7 cells treated with PDME and this effect was regulated by inhibition of HO-1 activity. These findings suggested that PDME functions as an HO-1 inducer and serves as an effective natural anti-inflammatory agent in LPS-induced inflammation.
PubMed: 38939180
DOI: 10.3892/etm.2024.12606 -
Frontiers in Cellular and Infection... 2024Hand, foot, and mouth disease (HFMD) is a common infectious disease caused by enterovirus 71 (EV71) that frequently affects children, leading to severe infections in...
Hand, foot, and mouth disease (HFMD) is a common infectious disease caused by enterovirus 71 (EV71) that frequently affects children, leading to severe infections in some cases. In general, when infection occurs, the body upregulates inflammatory responses to eliminate pathogenic microorganisms to protect the host from infection. However, EV71 may inhibit host's innate immunity to promote virus infection. At present, it is not fully understood how EV71 hijack the host cells for its own replication. Toll-like receptor 4 (TLR4), a natural immune receptor, historically associated with bacterial endotoxin-induced inflammatory responses. However, it is still unclear whether and how TLR4 is altered during EV71 infection. In this study, we observed a reduction in both TLR4 protein and gene transcript levels in RD, GES-1, and Vero cells following EV71 infection, as detected by RT-qPCR, immunofluorescence staining and western blot. Furthermore, we observed that the TLR4 downstream molecules of MYD88, p-NF-κB p65, p-TBK1 and related inflammatory cytokines were also reduced, suggesting that antiviral innate immune and inflammatory response were suppressed. To determine the impact of TLR4 changes on EV71 infection, we interfered EV71-infected RD cells with TLR4 agonist or inhibitor and the results showed that activation of TLR4 inhibited EV71 replication, while inhibition of TLR4 promote EV71 replication. Besides, EV71 replication was also promoted in TLR4 siRNA-transfected and EV71-infected RD cells. This suggests that down-regulation the expression of TLR4 by EV71 can inhibit host immune defense to promote EV71 self-replication. This novel mechanism may be a strategy for EV71 to evade host immunity.
Topics: Toll-Like Receptor 4; Enterovirus A, Human; Humans; Virus Replication; Signal Transduction; Animals; Vero Cells; Chlorocebus aethiops; Immunity, Innate; Host-Pathogen Interactions; Inflammation; Myeloid Differentiation Factor 88; Cell Line; Protein Serine-Threonine Kinases; Cytokines; NF-kappa B; Hand, Foot and Mouth Disease
PubMed: 38938877
DOI: 10.3389/fcimb.2024.1393680 -
Frontiers in Immunology 2024Human respiratory viruses are the most prevalent cause of disease in humans, with the highly infectious RSV being the leading cause of infant bronchiolitis and viral...
Human respiratory viruses are the most prevalent cause of disease in humans, with the highly infectious RSV being the leading cause of infant bronchiolitis and viral pneumonia. Responses to type I IFNs are the primary defense against viral infection. However, RSV proteins have been shown to antagonize type I IFN-mediated antiviral innate immunity, specifically dampening intracellular IFN signaling. Respiratory epithelial cells are the main target for RSV infection. In this study, we found RSV-NS1 interfered with the IFN-α JAK/STAT signaling pathway of epithelial cells. RSV-NS1 expression significantly enhanced IFN-α-mediated phosphorylation of STAT1, but not pSTAT2; and neither STAT1 nor STAT2 total protein levels were affected by RSV-NS1. However, expression of RSV-NS1 significantly reduced ISRE and GAS promoter activity and anti-viral IRG expression. Further mechanistic studies demonstrated RSV-NS1 bound STAT1, with protein modeling indicating a possible interaction site between STAT1 and RSV-NS1. Nuclear translocation of STAT1 was reduced in the presence of RSV-NS1. Additionally, STAT1's interaction with the nuclear transport adapter protein, KPNA1, was also reduced, suggesting a mechanism by which RSV blocks STAT1 nuclear translocation. Indeed, reducing STAT1's access to the nucleus may explain RSV's suppression of IFN JAK/STAT promoter activation and antiviral gene induction. Taken together these results describe a novel mechanism by which RSV controls antiviral IFN-α JAK/STAT responses, which enhances our understanding of RSV's respiratory disease progression.
Topics: STAT1 Transcription Factor; Humans; Signal Transduction; Interferon-alpha; Respiratory Syncytial Virus, Human; Viral Nonstructural Proteins; Respiratory Syncytial Virus Infections; Janus Kinases; Cell Nucleus; Phosphorylation; Active Transport, Cell Nucleus; Cell Line
PubMed: 38938568
DOI: 10.3389/fimmu.2024.1395809 -
Revue Medicale Suisse Jun 2024
Topics: Humans; Female; Male; Self Concept; Gender Identity; Anxiety Disorders
PubMed: 38938142
DOI: 10.53738/REVMED.2024.20.880.1279 -
BMC Plant Biology Jun 2024Anthracnose, mainly caused by Colletotrichum fructicola, leads to severe losses in pear production. However, there is limited information available regarding the...
BACKGROUND
Anthracnose, mainly caused by Colletotrichum fructicola, leads to severe losses in pear production. However, there is limited information available regarding the molecular response to anthracnose in pears.
RESULTS
In this study, the anthracnose-resistant variety 'Seli' and susceptible pear cultivar 'Cuiguan' were subjected to transcriptome analysis following C. fructicola inoculation at 6 and 24 h using RNA sequencing. A total of 3186 differentially expressed genes were detected in 'Seli' and 'Cuiguan' using Illumina sequencing technology. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analyses indicated that the transcriptional response of pears to C. fructicola infection included responses to reactive oxygen species, phytohormone signaling, phenylpropanoid biosynthesis, and secondary metabolite biosynthetic processes. Moreover, the mitogen-activated protein kinase (MAPK) signaling pathway and phenylpropanoid biosynthesis were involved in the defense of 'Seli'. Furthermore, the gene coexpression network data showed that genes related to plant-pathogen interactions were associated with C. fructicola resistance in 'Seli' at the early stage.
CONCLUSION
Our results showed that the activation of specific genes in MAPK, calcium signaling pathways and phenylpropanoid biosynthesis was highly related to C. fructicola resistance in 'Seli' and providing several potential candidate genes for breeding anthracnose-resistant pear varieties.
Topics: Pyrus; Colletotrichum; Plant Diseases; Disease Resistance; Gene Expression Profiling; Transcriptome; Gene Expression Regulation, Plant
PubMed: 38937683
DOI: 10.1186/s12870-024-05077-6 -
Behavior Therapy Jul 2024Sexual orientation and gender identity/expression change efforts (SOGIECEs) are discredited practices that are associated with serious negative effects and incompatible... (Review)
Review
Reckoning With Our Past and Righting Our Future: Report From the Behavior Therapy Task Force on Sexual Orientation and Gender Identity/Expression Change Efforts (SOGIECEs).
Sexual orientation and gender identity/expression change efforts (SOGIECEs) are discredited practices that are associated with serious negative effects and incompatible with modern standards for clinical practice. Despite evidence linking SOGIECEs with serious iatrogenic effects, and despite support for LGBTQ+-affirmative care alternatives, SOGIECE practices persist. In the 1970s and 1980s, Behavior Therapy published articles testing and/or endorsing SOGIECEs, thereby contributing to their overall development, acceptance, and use. The Behavior Therapy Task Force on SOGIECEs was assembled to conduct a rigorous review of the SOGIECE articles published in Behavior Therapy and to decide whether, and what, formal action(s) should be taken on these articles. This report provides a detailed review of the historic SOGIECE literature published in Behavior Therapy and outlines the Task Force's deliberative and democratic processes resulting in actions to: (1) add prominent advisory information to k = 24 SOGIECE papers in the form of digital "black box" disclaimers that caution readers that the SOGIECE practices tested or described in these papers are inconsistent with modern standards, (2) offset organizational financial benefits from the publication of these papers, and (3) promote LGBTQ+-affirmative practices. SOGIECEs are not the only concerning practices across the field's history, and the pages of today's scientific journals include practices that will be at odds with tomorrow's moral standards and ethical guidelines. This report calls for precautionary measures and editorial safeguards to minimize the future likelihood and impact of problematic published scholarship, including the need to fully include those with relevant lived experiences in all aspects of clinical science and peer review.
Topics: Humans; Sexual Behavior; Sexual and Gender Minorities; Gender Identity; Behavior Therapy; Advisory Committees; Female
PubMed: 38937042
DOI: 10.1016/j.beth.2024.05.006 -
Comparative Biochemistry and... Jun 2024The dramatic changes in the global climate pose a major threat to the survival of many organisms, including fish. To date, the regulatory mechanisms behind the...
The dramatic changes in the global climate pose a major threat to the survival of many organisms, including fish. To date, the regulatory mechanisms behind the physiological responses of fish to temperature changes have been studied, and a comprehensive analysis of the regulatory mechanisms of temperature tolerance will help to propose effective strategies for fish to cope with global warming. In this study, we investigated the expression profiles of proteins and metabolites in liver tissues of American shad (Alosa sapidissima) corresponding to different water temperatures (24 °C, 27 °C and 30 °C) at various times (1-month intervals) under natural culture conditions. Proteomic analysis showed that the expression levels of the heat shock protein family (e.g. HSPE1, HSP70, HSPA5 and HSPA.1) increase significantly with temperature and that many differentially expressed proteins were highly enriched especially in pathways related to the endoplasmic reticulum, oxidative phosphorylation and glycolysis/gluconeogenesis processes. In addition, the results of conjoint metabolomics and proteomics analysis suggested that the contents of several important amino acids and chemical compounds, including L-serine, L-isoleucine, L-cystine, choline and betaine, changed significantly under high-temperature environmental stress, affecting the metabolic levels of starch, amino acid and glucose, which is thought to represent a possible energy conservation method for A. sapidissima to cope with rapid changes in external temperature. In summary, our findings demonstrate that living under high temperatures for a long period of time leads to different physiological defense responses in A. sapidissima, which provides some new ideas for analyzing the molecular regulatory patterns of adaptation to high temperature and also provides a theoretical basis for the subsequent improvement of fish culture in response to global warming.
PubMed: 38936462
DOI: 10.1016/j.cbpa.2024.111686 -
Molecular Cell Jun 2024Innate immunity is essential for the host against pathogens, cancer, and autoimmunity. The innate immune system encodes many sensor, adaptor, and effector proteins and... (Review)
Review
Innate immunity is essential for the host against pathogens, cancer, and autoimmunity. The innate immune system encodes many sensor, adaptor, and effector proteins and relies on the assembly of higher-order signaling complexes to activate immune defense. Recent evidence demonstrates that many of the core complexes involved in innate immunity are organized as liquid-like condensates through a mechanism known as phase separation. Here, we discuss phase-separated condensates and their diverse functions. We compare the biochemical, structural, and mechanistic details of solid and liquid-like assemblies to explore the role of phase separation in innate immunity. We summarize the emerging evidence for the hypothesis that phase separation is a conserved mechanism that controls immune responses across the tree of life. The discovery of phase separation in innate immunity provides a new foundation to explain the rules that govern immune system activation and will enable the development of therapeutics to treat immune-related diseases properly.
PubMed: 38936362
DOI: 10.1016/j.molcel.2024.06.004 -
International Immunopharmacology Jun 2024Although cancer immunotherapy has become a successful therapeutic strategy in a certain range of solid cancer and hematological malignancies, this efficacy of... (Review)
Review
Although cancer immunotherapy has become a successful therapeutic strategy in a certain range of solid cancer and hematological malignancies, this efficacy of immunotherapy is impeded by limited success rates due to an immunologically "cold" state. The cGAS-STING signaling pathway is an evolutionarily conserved system which can find cytoplasmic DNA to regulate the innate immune and adaptive immune response. Beyond the host defense and autoimmune disorders, recent advances have now expanded the roles of cGAS-STING that is precise activated and tight regulated to improve anticancer immunity. Mounting evidence now has shown the crucial role of epigenetic regulation in mediating the expression of key genes associated with the cGAS-STING signaling pathway. In this review, we highlight the structure and cellular localization of cGAS and STING as well as intracellular cascade reaction of cGAS-STING signal transduction. We further summarize recent findings of epigenetic regulatory mechanisms that control the expression of cGAS and STING in cancer. The review aims to offer theoretical basis and reference for targeting the epigenetic mechanisms that control cGAS and STING gene expression to promote the development of more effective combination therapeutic regimens to enhance the efficacy of cancer immunotherapy in clinical practice and cancer clinical and cancer research workers.
PubMed: 38936059
DOI: 10.1016/j.intimp.2024.112556 -
Science (New York, N.Y.) Jun 2024
Topics: Humans; Brazil; Universities; Transsexualism; Transgender Persons; Policy
PubMed: 38935730
DOI: 10.1126/science.adp8278