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Journal of Clinical and Experimental... 2024Spontaneous bacterial peritonitis (SBP) is a common and serious complication in patients with decompensated cirrhosis. Precise quantification of bacterial DNA (bactDNA)...
BACKGROUND AND AIMS
Spontaneous bacterial peritonitis (SBP) is a common and serious complication in patients with decompensated cirrhosis. Precise quantification of bacterial DNA (bactDNA) and the related inflammatory response might add further information on the course of disease. The aim of the study was to evaluate the association between bactDNA, cytokine levels and clinical outcome.
METHODS
Ascites and serum samples of 98 patients with decompensated liver cirrhosis (42 with SBP and 56 without SBP) as well as serum samples of 21 healthy controls were collected. BactDNA in ascites and serum was detected and quantified by 16S rRNA PCR. Concentrations of IL-1β, TNF-α, IL-6, IL-8 and IL-10 were measured by a LEGENDplexTM multi-analyte flow assay. Clinical data were collected and analyzed retrospectively.
RESULTS
BactDNA was detected more frequently in ascites of patients with SBP ( = 24/42; 57.1%) than in ascites of patients without SBP ( = 5/56; 8.9%; < 0.001). Additionally, IL-6 levels in both ascites and serum were significantly higher in patients with SBP (ascites < 0.001, serum = 0.036). The quantity of bactDNA in ascites was strongly correlated with polymorphonuclear neutrophil count in ascites (r = 0.755; < 0.001) as well as ascites IL-6 levels (r = 0.399; < 0.001). Receiver operating characteristic (ROC) curve analysis to diagnose SBP provided an AUC of 0.764 (95% CI: 0.661-0.867) for serum IL-6 levels, an AUC of 0.810 (95% CI: 0.714-0.905) for ascites IL-6 levels, and an AUC of 0.755 (95% CI: 0.651-0.858) for bactDNA levels in ascites.
CONCLUSIONS
The correlation between the amount of bactDNA and IL-6 confirms the pathophysiological relevance of bactDNA and IL-6 as potential biomarkers for the diagnosis of SBP.
PubMed: 38962151
DOI: 10.1016/j.jceh.2024.101434 -
Frontiers in Microbiology 2024Marine bacterioplankton play a crucial role in the cycling of carbon, nitrogen, and phosphorus in coastal waters. And the impact of environmental factors on bacterial...
Marine bacterioplankton play a crucial role in the cycling of carbon, nitrogen, and phosphorus in coastal waters. And the impact of environmental factors on bacterial community structure and ecological functions is a dynamic ongoing process. To systematically assess the relationship between environmental changes and bacterioplankton communities, this study delved into the spatiotemporal distribution and predicted metabolic characteristics of bacterioplankton communities at two estuarine beaches in Northern China. Coastal water samples were collected regularly in spring, summer, and autumn, and were analyzed in combination with environmental parameters and bacterioplankton community. Results indicated significant seasonal variations in bacterioplankton communities as Bacteroidetes and Actinobacteria were enriched in spring, Cyanobacteria proliferated in summer. While Pseudomonadota and microorganisms associated with organic matter decomposition prevailed in autumn, closely linked to seasonal variation of temperature, light and nutrients such as nitrogen and phosphorus. Particularly in summer, increased tourism activities and riverine inputs significantly raised nutrient levels, promoting the proliferation of specific photosynthetic microorganisms, potentially linked to the occurrence of phytoplankton blooms. Spearman correlation analysis further revealed significant correlations between bacterioplankton communities and environmental factors such as salinity, chlorophyll , and total dissolved phosphorus (TDP). Additionally, the metabolic features of the spring bacterioplankton community were primarily characterized by enhanced activities in the prokaryotic carbon fixation pathways, reflecting rapid adaptation to increased light and temperature, as well as significant contributions to primary productivity. In summer, the bacterial communities were involved in enhanced glycolysis and biosynthetic pathways, reflecting high energy metabolism and responses to increased light and biomass. In autumn, microorganisms adapted to the accelerated decomposition of organic matter and the seasonal changes in environmental conditions through enhanced amino acid metabolism and material cycling pathways. These findings demonstrate that seasonal changes and human activities significantly influence the structure and function of bacterioplankton communities by altering nutrient dynamics and physical environmental conditions. This study provides important scientific insights into the marine biological responses under global change.
PubMed: 38962120
DOI: 10.3389/fmicb.2024.1431548 -
Chinese Medical Journal Pulmonary and... Jun 2024Idiopathic pulmonary fibrosis (IPF) is a chronic and progressive interstitial lung disease with a dismal prognosis. Early diagnosis, accurate prognosis, and personalized...
Idiopathic pulmonary fibrosis (IPF) is a chronic and progressive interstitial lung disease with a dismal prognosis. Early diagnosis, accurate prognosis, and personalized therapeutic interventions are essential for improving patient outcomes. Biomarkers, as measurable indicators of biological processes or disease states, hold significant promise in IPF management. In recent years, there has been a growing interest in identifying and validating biomarkers for IPF, encompassing various molecular, imaging, and clinical approaches. This review provides an in-depth examination of the current landscape of IPF biomarker research, highlighting their potential applications in disease diagnosis, prognosis, and treatment response. Additionally, the challenges and future perspectives of biomarker integration into clinical practice for precision medicine in IPF are discussed.
PubMed: 38962100
DOI: 10.1016/j.pccm.2024.04.003 -
International Cancer Conference Journal Jul 2024A 61-year-old woman with pathogenic variant had been treated for 20 years and showed dynamic changes in the genomic profile of her metachronous bilateral breast cancer...
A 61-year-old woman with pathogenic variant had been treated for 20 years and showed dynamic changes in the genomic profile of her metachronous bilateral breast cancer and metastases. She underwent right breast conservation surgery at age 42-Genome 1, lung metastasis and left axillary lymph node metastasis at age 51, partial excision under local anesthesia for left breast cancer at age 53-Genome 2, left axillary lymph node dissection was added 6 month later-Genome 3. Then, olaparib was administered, and subsequently, left mastectomy was performed for the recurrence of left breast cancer at age 59-Genome 4. Genomic profile of the tumor was analyzed at four points (Genome 1-3 were analyzed by in house breast cancer panel, and Genome 4 was analyzed by Foundation One CDx). Two interesting findings emerged from these analyses. First, the genomic profile revealed that the left axillary lymph node metastasis, considered histologically from right breast cancer, was a metastasis from the left breast cancer. The second finding is that as the disease progressed, mutation profile became more diverse. The profile of the left breast cancer removed after olaparib and other treatments showed reversion mutation of and was diagnosed as tumor mutation burden high. Subsequent response to pembrolizumab was favorable.
PubMed: 38962040
DOI: 10.1007/s13691-024-00685-3 -
Frontiers in Immunology 2024In the Americas, is the predominant causative species of malaria, a debilitating and economically significant disease. Due to the complexity of the malaria parasite...
In the Americas, is the predominant causative species of malaria, a debilitating and economically significant disease. Due to the complexity of the malaria parasite life cycle, a vaccine formulation with multiple antigens expressed in various parasite stages may represent an effective approach. Based on this, we previously designed and constructed a chimeric recombinant protein, PvRMC-1, composed by PvCyRPA, PvCelTOS, and Pvs25 epitopes. This chimeric protein was strongly recognized by naturally acquired antibodies from exposed population in the Brazilian Amazon. However, there was no investigation about the induced immune response of PvRMC-1. Therefore, in this work, we evaluated the immunogenicity of this chimeric antigen formulated in three distinct adjuvants: Stimune, AddaVax or Aluminum hydroxide (Al(OH)3) in BALB/c mice. Our results suggested that the chimeric protein PvRMC-1 were capable to generate humoral and cellular responses across all three formulations. Antibodies recognized full-length PvRMC-1 and linear B-cell epitopes from PvCyRPA, PvCelTOS, and Pvs25 individually. Moreover, mice's splenocytes were activated, producing IFN-γ in response to PvCelTOS and PvCyRPA peptide epitopes, affirming T-cell epitopes in the antigen. While aluminum hydroxide showed notable cellular response, Stimune and Addavax induced a more comprehensive immune response, encompassing both cellular and humoral components. Thus, our findings indicate that PvRMC-1 would be a promising multistage vaccine candidate that could advance to further preclinical studies.
Topics: Animals; Plasmodium vivax; Mice; Antigens, Protozoan; Malaria, Vivax; Antibodies, Protozoan; Mice, Inbred BALB C; Malaria Vaccines; Female; Protozoan Proteins; Epitopes, B-Lymphocyte; Recombinant Fusion Proteins; Disease Models, Animal; Adjuvants, Immunologic; Immunogenicity, Vaccine; Antigens, Surface
PubMed: 38962015
DOI: 10.3389/fimmu.2024.1392043 -
Frontiers in Immunology 2024Autoimmune diseases (AID) have emerged as prominent contributors to disability and mortality worldwide, characterized by intricate pathogenic mechanisms involving... (Review)
Review
Autoimmune diseases (AID) have emerged as prominent contributors to disability and mortality worldwide, characterized by intricate pathogenic mechanisms involving genetic, environmental, and autoimmune factors. In response to this challenge, a growing body of research in recent years has delved into genetic modifications, yielding valuable insights into AID prevention and treatment. Sirtuins (SIRTs) constitute a class of NAD-dependent histone deacetylases that orchestrate deacetylation processes, wielding significant regulatory influence over cellular metabolism, oxidative stress, immune response, apoptosis, and aging through epigenetic modifications. Resveratrol, the pioneering activator of the SIRTs family, and its derivatives have captured global scholarly interest. In the context of AID, these compounds hold promise for therapeutic intervention by modulating the SIRTs pathway, impacting immune cell functionality, suppressing the release of inflammatory mediators, and mitigating tissue damage. This review endeavors to explore the potential of resveratrol and its derivatives in AID treatment, elucidating their mechanisms of action and providing a comprehensive analysis of current research advancements and obstacles. Through a thorough examination of existing literature, our objective is to advocate for the utilization of resveratrol and its derivatives in AID treatment while offering crucial insights for the formulation of innovative therapeutic approaches.
Topics: Resveratrol; Humans; Autoimmune Diseases; Animals; Sirtuins
PubMed: 38962006
DOI: 10.3389/fimmu.2024.1390907 -
Frontiers in Immunology 2024Fibroblast growth factors (FGFs) are a versatile family of peptide growth factors that are involved in various biological functions, including cell growth and... (Review)
Review
Fibroblast growth factors (FGFs) are a versatile family of peptide growth factors that are involved in various biological functions, including cell growth and differentiation, embryonic development, angiogenesis, and metabolism. Abnormal FGF/FGF receptor (FGFR) signaling has been implicated in the pathogenesis of multiple diseases such as cancer, metabolic diseases, and inflammatory diseases. It is worth noting that macrophage polarization, which involves distinct functional phenotypes, plays a crucial role in tissue repair, homeostasis maintenance, and immune responses. Recent evidence suggests that FGF/FGFR signaling closely participates in the polarization of macrophages, indicating that they could be potential targets for therapeutic manipulation of diseases associated with dysfunctional macrophages. In this article, we provide an overview of the structure, function, and downstream regulatory pathways of FGFs, as well as crosstalk between FGF signaling and macrophage polarization. Additionally, we summarize the potential application of harnessing FGF signaling to modulate macrophage polarization.
Topics: Humans; Macrophages; Signal Transduction; Fibroblast Growth Factors; Animals; Receptors, Fibroblast Growth Factor; Macrophage Activation; Inflammation
PubMed: 38962005
DOI: 10.3389/fimmu.2024.1390453 -
An emerging maestro of immune regulation: how DOT1L orchestrates the harmonies of the immune system.Frontiers in Immunology 2024The immune system comprises a complex yet tightly regulated network of cells and molecules that play a critical role in protecting the body from infection and disease.... (Review)
Review
The immune system comprises a complex yet tightly regulated network of cells and molecules that play a critical role in protecting the body from infection and disease. The activity and development of each immune cell is regulated in a myriad of ways including through the cytokine milieu, the availability of key receptors, via tailored intracellular signalling cascades, dedicated transcription factors and even by directly modulating gene accessibility and expression; the latter is more commonly known as epigenetic regulation. In recent years, epigenetic regulators have begun to emerge as key players involved in modulating the immune system. Among these, the lysine methyltransferase DOT1L has gained significant attention for its involvement in orchestrating immune cell formation and function. In this review we provide an overview of the role of DOT1L across the immune system and the implications of this role on health and disease. We begin by elucidating the general mechanisms of DOT1L-mediated histone methylation and its impact on gene expression within immune cells. Subsequently, we provide a detailed and comprehensive overview of recent studies that identify DOT1L as a crucial regulator of immune cell development, differentiation, and activation. Next, we discuss the potential mechanisms of DOT1L-mediated regulation of immune cell function and shed light on how DOT1L might be contributing to immune cell homeostasis and dysfunction. We then provide food for thought by highlighting some of the current obstacles and technical limitations precluding a more in-depth elucidation of DOT1L's role. Finally, we explore the potential therapeutic implications of targeting DOT1L in the context of immune-related diseases and discuss ongoing research efforts to this end. Overall, this review consolidates the current paradigm regarding DOT1L's role across the immune network and emphasises its critical role in governing the healthy immune system and its potential as a novel therapeutic target for immune-related diseases. A deeper understanding of DOT1L's immunomodulatory functions could pave the way for innovative therapeutic approaches which fine-tune the immune response to enhance or restore human health.
Topics: Humans; Histone-Lysine N-Methyltransferase; Animals; Epigenesis, Genetic; Immune System; Immunomodulation; Histones
PubMed: 38962004
DOI: 10.3389/fimmu.2024.1385319 -
Heliyon Jun 2024Anaplastic lymphoma kinase (ALK) inhibitors are the recommended treatment of -rearranged non-small cell lung cancer but are prone to eventual drug resistance. Herein we...
Anaplastic lymphoma kinase (ALK) inhibitors are the recommended treatment of -rearranged non-small cell lung cancer but are prone to eventual drug resistance. Herein we report a 45-year-old Asian woman diagnosed with rearranged lung adenocarcinoma. Small cell lung cancer-like phenotypic transformation occurred when resistance to crizotinib treatment. Next-generation sequencing was performed and detected an rearrangement co-existent with a gene mutation in the small cell specimens. The patient had a good response to alectinib with a progression-free survival >7 months. After disease progression, newly emerged and gene mutations co-existent with rearrangement were detected. The patient had a good initial response to ceritinib treatment, which last for >12 months. After ceritinib failure, however, more complicated mutations within the ALK kinase domain (, , newly emerged and ) were detected. Ultimately, due to terminal rapid progression and resistance to lorlatinib, the overall survival was nearly 3 years. Our case showed that next-generation ALK-tyrosine kinase inhibitors (TKIs) may be an appropriate choice after transformation to small cell lung cancer and failure to one ALK-TKI. Sequential biopsies and gene mutation monitoring are important to arrange the sequence of different generation ALK-TKIs. Appropriate sequential therapies may yield a prolonged response with a satisfactory quality of life in patients with advanced -rearranged non-small cell lung cancer.
PubMed: 38961982
DOI: 10.1016/j.heliyon.2024.e32030 -
Heliyon Jun 2024Emerging evidence has illuminated the pivotal role of long noncoding RNAs (lncRNAs) in orchestrating immunological functions and autoimmune responses. In the context of... (Review)
Review
Emerging evidence has illuminated the pivotal role of long noncoding RNAs (lncRNAs) in orchestrating immunological functions and autoimmune responses. In the context of Crohn's disease (CD), an array of novel lncRNAs has been identified in the plasma and intestinal tissues of afflicted individuals, suggesting a dualistic influence on the disease progression, either exacerbating or mitigating its course. Current research has demonstrated the involvement of lncRNAs in competitive endogenous RNA, the inflammation process, epithelial barrier function, gut microbiota imbalance, and epigenetic regulation. This review aims to encapsulate the current knowledge on the lncRNA contribution to CD and underscore potential avenues for future research. LncRNAs are increasingly recognized as significant biomarkers and potential therapeutic targets, holding a key position in the pathogenesis of CD. Furthermore, the unique attributes of circulating lncRNAs, such as minimal side effects, combinational therapy potential, and personalized medicine, render them as promising therapeutic tools for individual health management in CD.
PubMed: 38961978
DOI: 10.1016/j.heliyon.2024.e32606