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Immunological Reviews Jan 2023C3 is the central effector molecule of the complement system, mediating its multiple functions through different binding sites and their corresponding receptors. We will... (Review)
Review
C3 is the central effector molecule of the complement system, mediating its multiple functions through different binding sites and their corresponding receptors. We will introduce the C3 forms (native C3, C3 [H O], and intracellular C3), the C3 fragments C3a, C3b, iC3b, and C3dg/C3d, and the C3 expression sites. To highlight the important role that C3 plays in human biological processes, we will give an overview of the diseases linked to C3 deficiency and to uncontrolled C3 activation. Next, we will present a structural description of C3 activation and of the C3 fragments generated by complement regulation. We will proceed by describing the C3a interaction with the anaphylatoxin receptor, followed by the interactions of opsonins (C3b, iC3b, and C3dg/C3d) with complement receptors, divided into two groups: receptors bearing complement regulatory functions and the effector receptors without complement regulatory activity. We outline the molecular architecture of the receptors, their binding sites on the C3 activation fragments, the cells expressing them, the diversity of their functions, and recent advances. With this review, we aim to give an up-to-date analysis of the processes triggered by C3 activation fragments on different cell types in health and disease contexts.
Topics: Humans; Complement C3; Complement C3b; Receptors, Complement; Binding Sites; Complement Activation
PubMed: 36271889
DOI: 10.1111/imr.13147 -
Frontiers in Immunology 2021Persistent hyper-inflammation is a distinguishing pathophysiological characteristic of chronic wounds, and macrophage malfunction is considered as a major contributor... (Review)
Review
Persistent hyper-inflammation is a distinguishing pathophysiological characteristic of chronic wounds, and macrophage malfunction is considered as a major contributor thereof. In this review, we describe the origin and heterogeneity of macrophages during wound healing, and compare macrophage function in healing and non-healing wounds. We consider extrinsic and intrinsic factors driving wound macrophage dysregulation, and review systemic and topical therapeutic approaches for the restoration of macrophage response. Multidimensional analysis is highlighted through the integration of various high-throughput technologies, used to assess the diversity and activation states as well as cellular communication of macrophages in healing and non-healing wound. This research fills the gaps in current literature and provides the promising therapeutic interventions for chronic wounds.
Topics: Animals; Biomarkers; Chronic Disease; Humans; Inflammation; Macrophage Activation; Macrophages; Regeneration; Wound Healing
PubMed: 34220830
DOI: 10.3389/fimmu.2021.681710 -
Sports Health Mar 2021The hamstring muscles play a critical role in the prevention of lower limb injuries. However, it is still unclear which exercises are more effective in terms of muscle...
BACKGROUND
The hamstring muscles play a critical role in the prevention of lower limb injuries. However, it is still unclear which exercises are more effective in terms of muscle activation.
HYPOTHESIS
In healthy individuals, there are differences between muscular activations of the biceps femoris (BF), semitendinosus (ST), and semimembranosus (SM) muscles during eccentric hamstring exercises.
STUDY DESIGN
Cross-sectional.
LEVEL OF EVIDENCE
Level 2.
METHODS
A total of 31 healthy participants (18 male; mean age, 22.5 years; SD, 3.1) were included in this study. The maximum voluntary isometric contraction of the hamstring muscles was measured using an isokinetic dynamometer. The participants were asked to perform one of the following exercises randomly (3 repetitions each): stiff-leg deadlift (SLDL), unilateral stiff-leg deadlift (USLDL), Nordic hamstring exercise (NHE), and ball leg curl (BLC). Activation of the BF, ST, and SM muscles was measured using surface electromyography during the exercises. In the statistical analysis of this study, factorial analysis of variance was used to compare the effects of each exercise on the muscle groups and to analyze which exercise type was more effective for each muscle group.
RESULTS
The NHE led to higher muscle activation than the other exercises ( < 0.001). When exercise type and muscle interaction were examined, SM activation was lower than BF ( = 0.04) and ST ( = 0.001) during NHE ( < 0.05). The highest level of muscular activation was recorded during the NHE in both male and female participants.
CONCLUSION
The NHE may be the most effective exercise for the hamstring muscles as it leads to greater muscle activation. SLDL, USLDL, and BLC exercises may be preferred at the beginning of strength training programs since they lead to lower muscular activation compared with the NHE.
CLINICAL RELEVANCE
To select the optimum hamstring exercise, it is important to know the activation levels of the hamstring muscles during different eccentric exercises.
Topics: Cross-Sectional Studies; Electromyography; Female; Hamstring Muscles; Humans; Male; Muscle Contraction; Physical Conditioning, Human; Resistance Training; Young Adult
PubMed: 32857686
DOI: 10.1177/1941738120938649 -
Journal of the International Society of... Oct 2020Despite a substantial body of research, no clear best practice guidelines exist for the assessment of hydration in athletes. Body water is stored in and shifted between... (Review)
Review
BACKGROUND
Despite a substantial body of research, no clear best practice guidelines exist for the assessment of hydration in athletes. Body water is stored in and shifted between different sites throughout the body complicating hydration assessment. This review seeks to highlight the unique strengths and limitations of various hydration assessment methods described in the literature as well as providing best practice guidelines.
MAIN BODY
There is a plethora of methods that range in validity and reliability, including complicated and invasive methods (i.e. neutron activation analysis and stable isotope dilution), to moderately invasive blood, urine and salivary variables, progressing to non-invasive metrics such as tear osmolality, body mass, bioimpedance analysis, and sensation of thirst. Any single assessment of hydration status is problematic. Instead, the recommended approach is to use a combination, which have complementary strengths, which increase accuracy and validity. If methods such as salivary variables, urine colour, vital signs and sensation of thirst are utilised in isolation, great care must be taken due to their lack of sensitivity, reliability and/or accuracy. Detailed assessments such as neutron activation and stable isotope dilution analysis are highly accurate but expensive, with significant time delays due to data analysis providing little potential for immediate action. While alternative variables such as hormonal and electrolyte concentration, bioimpedance and tear osmolality require further research to determine their validity and reliability before inclusion into any test battery.
CONCLUSION
To improve best practice additional comprehensive research is required to further the scientific understanding of evaluating hydration status.
Topics: Absorptiometry, Photon; Blood Physiological Phenomena; Body Mass Index; Body Water; Dehydration; Drinking; Electric Impedance; Hematocrit; Hormones; Humans; Neutron Activation Analysis; Osmolar Concentration; Saliva; Serum; Sodium; Sports; Tears; Thirst; Urinalysis; Vital Signs
PubMed: 33126891
DOI: 10.1186/s12970-020-00381-6 -
Blood Advances Apr 2020Human natural killer (NK) cells in peripheral blood perform many functions, and classification of specific subsets has been a longstanding goal. We report single-cell...
Human natural killer (NK) cells in peripheral blood perform many functions, and classification of specific subsets has been a longstanding goal. We report single-cell RNA sequencing of NK cells, comparing gene expression in unstimulated and interleukin (IL)-2-activated cells from healthy cytomegalovirus (CMV)-negative donors. Three NK cell subsets resembled well-described populations; CD56brightCD16-, CD56dimCD16+CD57-, and CD56dimCD16+CD57+. CD56dimCD16+CD57- cells subdivided to include a population with higher chemokine mRNA and increased frequency of killer-cell immunoglobulin-like receptor expression. Three novel human blood NK cell populations were identified: a population of type I interferon-responding NK cells that were CD56neg; a population exhibiting a cytokine-induced memory-like phenotype, including increased granzyme B mRNA in response to IL-2; and finally, a small population, with low ribosomal expression, downregulation of oxidative phosphorylation, and high levels of immediate early response genes indicative of cellular activation. Analysis of CMV+ donors established that CMV altered the proportion of NK cells in each subset, especially an increase in adaptive NK cells, as well as gene regulation within each subset. Together, these data establish an unexpected diversity in blood NK cells and provide a new framework for analyzing NK cell responses in health and disease.
Topics: Cytomegalovirus; Cytomegalovirus Infections; Humans; Killer Cells, Natural; Receptors, KIR; Sequence Analysis, RNA
PubMed: 32271902
DOI: 10.1182/bloodadvances.2019000699 -
Journal of Advanced Research Feb 2023Increasing evidence demonstrates that the activation states and diverse spectrum of macrophage subtypes display dynamic heterogeneity in the tumor microenvironment,...
Integrated immunogenomic analysis of single-cell and bulk tissue transcriptome profiling unravels a macrophage activation paradigm associated with immunologically and clinically distinct behaviors in ovarian cancer.
INTRODUCTION
Increasing evidence demonstrates that the activation states and diverse spectrum of macrophage subtypes display dynamic heterogeneity in the tumor microenvironment, which plays a critical role in a variety of cancer types.
OBJECTIVES
To investigate the heterogeneity and the homeostasis of different macrophage subtypes, as well as their effect on biological and clinical manifestations of ovarian cancer (OV).
METHOD
Integrated immunogenomic analysis of single-cell and bulk tissuetranscriptome profiling was performed to systematically investigate the association between macrophage activation and prognostic and therapeutic efficacy. Consensus clustering analysis was used to define novel macrophage subtypes. An artificial neural network was used to simulate the dynamic activation of macrophages.
RESULTS
The pan-cohort results suggested that high relative infiltration abundance of M0 and M1 macrophages was associated with improved outcome and therapeutic efficacy. However, it was the opposite for M2 macrophages. Unsupervised consensus clustering analysis revealed two OV subgroups characterized by a balance between M0, M1 and M2 macrophages with distinct clinical and immunological behaviors. Finally, a macrophage polarization-derived artificial neural network model was proposed to serve as a robust prognostic factor and predictive biomarker for therapeutic efficacy, which was validated in different independent patient cohorts.
CONCLUSION
The present study provides a new understanding of macrophage heterogeneity and its association with OV prognosis and underlines the future clinical potential of a macrophage activation model for tumor prevention and treatment.
Topics: Humans; Female; Macrophage Activation; Macrophages; Transcriptome; Gene Expression Profiling; Ovarian Neoplasms; Tumor Microenvironment
PubMed: 36725186
DOI: 10.1016/j.jare.2022.04.006 -
Cell Reports Sep 2020Single-nucleus RNA sequencing (snRNA-seq) is used as an alternative to single-cell RNA-seq, as it allows transcriptomic profiling of frozen tissue. However, it is...
Single-nucleus RNA sequencing (snRNA-seq) is used as an alternative to single-cell RNA-seq, as it allows transcriptomic profiling of frozen tissue. However, it is unclear whether snRNA-seq is able to detect cellular state in human tissue. Indeed, snRNA-seq analyses of human brain samples have failed to detect a consistent microglial activation signature in Alzheimer's disease. Our comparison of microglia from single cells and single nuclei of four human subjects reveals that, although most genes show similar relative abundances in cells and nuclei, a small population of genes (∼1%) is depleted in nuclei compared to whole cells. This population is enriched for genes previously implicated in microglial activation, including APOE, CST3, SPP1, and CD74, comprising 18% of previously identified microglial-disease-associated genes. Given the low sensitivity of snRNA-seq to detect many activation genes, we conclude that snRNA-seq is not suited for detecting cellular activation in microglia in human disease.
Topics: Gene Expression Profiling; Humans; Microglia; Sequence Analysis, RNA; Single-Cell Analysis
PubMed: 32997994
DOI: 10.1016/j.celrep.2020.108189 -
Frontiers in Immunology 2019T-regulatory cells (Tregs) represent a unique subpopulation of helper T-cells by maintaining immune equilibrium using various mechanisms. The role of T-cell receptors... (Review)
Review
T-regulatory cells (Tregs) represent a unique subpopulation of helper T-cells by maintaining immune equilibrium using various mechanisms. The role of T-cell receptors (TCR) in providing homeostasis and activation of conventional T-cells is well-known; however, for Tregs, this area is understudied. In the last two decades, evidence has accumulated to confirm the importance of the TCR in Treg homeostasis and antigen-specific immune response regulation. In this review, we describe the current view of Treg subset heterogeneity, homeostasis and function in the context of TCR involvement. Recent studies of the TCR repertoire of Tregs, combined with single-cell gene expression analysis, revealed the importance of TCR specificity in shaping Treg phenotype diversity, their functions and homeostatic maintenance in various tissues. We propose that Tregs, like conventional T-helper cells, act to a great extent in an antigen-specific manner, which is provided by a specific distribution of Tregs in niches.
Topics: Animals; Homeostasis; Humans; Lymphocyte Activation; Receptors, Antigen, T-Cell; T-Lymphocytes, Regulatory
PubMed: 31993063
DOI: 10.3389/fimmu.2019.03100 -
Molecules (Basel, Switzerland) Mar 2021Conditionally activated ("caged") oligonucleotides provide useful spatiotemporal control for studying dynamic biological processes, e.g., regulating in vivo gene... (Review)
Review
Conditionally activated ("caged") oligonucleotides provide useful spatiotemporal control for studying dynamic biological processes, e.g., regulating in vivo gene expression or probing specific oligonucleotide targets. This review summarizes recent advances in caging strategies, which involve different stimuli in the activation step. Oligo cyclization is a particularly attractive caging strategy, which simplifies the probe design and affords oligo stabilization. Our laboratory developed an efficient synthesis for circular caged oligos, and a circular caged antisense DNA oligo was successfully applied in gene regulation. A second technology is Transcriptome In Vivo Analysis (TIVA), where caged oligos enable mRNA isolation from single cells in living tissue. We highlight our development of TIVA probes with improved caging stability. Finally, we illustrate the first protease-activated oligo probe, which was designed for caspase-3. This expands the toolkit for investigating the transcriptome under a specific physiologic condition (e.g., apoptosis), particularly in specimens where light activation is impractical.
Topics: Animals; Cyclization; Enzyme Activation; Gene Expression; Gene Expression Profiling; Gene Expression Regulation; Humans; Light; Oligonucleotides; Oligonucleotides, Antisense; RNA, Messenger; Synthetic Biology
PubMed: 33803234
DOI: 10.3390/molecules26051481 -
Scientific Data Dec 2023The UCLA Cosmochemistry Database was initiated as part of a data-rescue and -storage project aimed at archiving a variety of cosmochemical data acquired at University of...
The UCLA Cosmochemistry Database was initiated as part of a data-rescue and -storage project aimed at archiving a variety of cosmochemical data acquired at University of California, Los Angeles (UCLA). The data collection includes elemental compositions of extraterrestrial materials analyzed by UCLA cosmochemists over the last five decades. The analytical techniques include atomic absorption spectrometry (AAS) and neutron activation analysis (NAA) at UCLA. The data collection is stored on the Astromaterials Data System (Astromat). We provide both interactive tables and downloadable datasheets for users to access all data. The UCLA Cosmochemistry Database archives cosmochemical data that are essential tools for increasing our understanding of the nature and origin of extraterrestrial materials. Future studies can reference the data collection in the examination, analysis, and classification of newly acquired extraterrestrial samples.
PubMed: 38062064
DOI: 10.1038/s41597-023-02807-7