Complement receptor 3

Environmental toxicants overwhelmingly occur together as mixtures. The variety of possible chemical interactions makes it difficult to predict the danger of the mixture. In this work, we propose the novel Reflected Generalized Concentration Addition (RGCA), a piece-wise, geometric technique for sigmoidal dose-responsed inverse functions that extends the use of generalized concentration addition (GCA) for 3+ parameter models. Since experimental tests of all relevant mixtures is costly and intractable, we rely only on the individual chemical dose responses...

BACKGROUND: The purpose of this narrative review is to describe the mechanisms that are responsible for the development of infertility and PCOS, with a focus on the role of obesity, insulin sensitivity and treatment with metformin and GLP-1s. METHODS: The relevant publications were identified after systematic queries of the following sources: PubMed, Google Scholar, Web of Science, and publishers' databases, complemented by a cross-check of the reference lists. We used a combination of the search terms "polycystic ovary syndrome", "obesity" and "insulin resistance" with "metformin", "exenatide", "liraglutide", "semaglutide", "orlistat" and terms relevant to the topic of each paragraph (e...

Conn's syndrome, defined as unilateral aldosterone-producing adenoma, accounts for 35-40% of cases of primary hyperaldosteronism. Primary hyperaldosteronism typically occurs in younger patients with poorly controlled arterial hypertension due to extracellular fluid retention, in whom at least a triple combination of antihypertensives, including a diuretic, is needed to maintain normotension. The clinical picture of arterial hypertension may be complemented by symptoms associated with hypokalaemia, such as weakness, fatigue, palpitations, convulsions, polydipsia, or polyuria...

INTRODUCTION: Myasthenia gravis (MG) is an autoimmune condition targeting the neuromuscular junction, which manifests with neuromuscular symptoms of varying severity and significant morbidity. The mainstay of treatment in MG is mitigation of the immune cascade with steroids and non-steroidal immunosuppressive therapies. The therapeutic strategies in MG are transitioning from broad and indiscriminate immunosuppression to novel agents targeting key steps in MG pathogenesis, including T cell activation, B cell proliferation, complement activation, maintenance of pathogenic antibody production, and proinflammatory cytokine production...

Dysregulation of the host immune response has a central role in the pathophysiology of sepsis. There has been much interest in immunomodulatory drugs as potential therapeutic adjuncts in sepsis. We conducted a systematic review and meta-analysis of randomised controlled trials evaluating the safety and clinical effectiveness of immunomodulatory drugs as adjuncts to standard care in the treatment of adults with sepsis. Our primary outcomes were serious adverse events and all-cause mortality. Fifty-six unique, eligible randomised controlled trials were identified, assessing a range of interventions including cytokine inhibitors; anti-inflammatories; immune cell stimulators; platelet pathway inhibitors; and complement inhibitors...

Bacillus anthracis peptidoglycan (PGN) is a major component of the bacterial cell wall and a key pathogen-associated molecular pattern contributing to anthrax pathology, including organ dysfunction and coagulopathy. Increases in apoptotic leukocytes are a late-stage feature of anthrax and sepsis, suggesting there is a defect in apoptotic clearance. In this study, we tested the hypothesis that B. anthracis PGN inhibits the capacity of human monocyte-derived macrophages (MΦ) to efferocytose apoptotic cells...

NSD3 is a member of six H3K36-specific histone lysine methyltransferases in metazoans. Its overexpression or mutation is implicated in developmental defects and oncogenesis. Aside from the well-characterized catalytic SET domain, NSD3 has multiple clinically relevant potential chromatin-binding motifs, such as the proline-tryptophan-tryptophan-proline (PWWP), the plant homeodomain (PHD), and the adjacent Cys-His-rich domain located at the C-terminus. The crystal structure of the individual domains is available, and this structural knowledge has allowed the designing of potential inhibitors, but the intrinsic flexibility of larger constructs has hindered the characterization of mutual domain conformations...

Objective: To evaluate the mid-term efficacy of ABO incompatible living donor kidney transplantation (ABOi-KT) based on the results of routine renal biopsy for transplantation. Methods: Retrospective collection of clinical data from 23 pairs of ABOi-KT donors and recipients at the First Affiliated Hospital of Sun Yat-sen University from July 2015 to November 2021. ABOi-KT was performed on recipients after desensitization treatment, and the results of routine kidney transplant biopsy at 1 week, 1 month, 3 months, 6 months, and 12 months after surgery were analyzed...

After myocardial infarction (MI), mammalian hearts do not regenerate, and the microenvironment is disrupted. Hippo signaling loss of function with activation of transcriptional co-factor YAP induces heart renewal and rebuilds the post-MI microenvironment. In this study, we investigated adult renewal-competent mouse hearts expressing an active version of YAP, called YAP5SA, in cardiomyocytes (CMs). Spatial transcriptomics and single-cell RNA sequencing revealed a conserved, renewal-competent CM cell state called adult (a)CM2 with high YAP activity...

As an endocrine cytokine, fibroblast growth factor 21 (FGF21) exhibits anti-inflammatory properties. With the development of lupus nephritis (LN), which is tightly related to pathogenic factors, including inflammation and immune cell dysregulation, we explored the impact of Fibroblast Growth Factor 21 (FGF21) as well as its underlying mechanism. We induced an in vivo LN model using pristane in both wild-type C57BL/6 and FGF21 knockout (FGF21-/- ) mice. LN serum obtained from 32-week-old wild-type LN mice was used to stimulate RAW264...

BACKGROUND AND OBJECTIVES: Antibodies (Abs) specific for the low-density lipoprotein receptor-related protein 4 (LRP4) occur in up to 5% of patients with myasthenia gravis (MG). The objective of this study was to profile LRP4-Ab effector actions. METHODS: We evaluated the efficacy of LRP4-specific compared with AChR-specific IgG to induce Ab-dependent cellular phagocytosis (ADCP), Ab-dependent cellular cytotoxicity (ADCC), and Ab-dependent complement deposition (ADCD)...

X-ray crystallography has for most of the last century been the standard technique to determine the high-resolution structure of biological macromolecules, including multi-subunit protein-protein and protein-nucleic acids as large as the ribosome and viruses. As such, the successful application of X-ray crystallography to many biological problems revolutionized biology and biomedicine by solving the structures of small molecules and vitamins, peptides and proteins, DNA and RNA molecules, and many complexes-affording a detailed knowledge of the structures that clarified biological and chemical mechanisms, conformational changes, interactions, catalysis and the biological processes underlying DNA replication, translation, and protein synthesis...

Staphylococcus aureus is the most common pathogen that causes implant-associated osteomyelitis, a clinically incurable disease. Immune evasion of S. aureus relies on various mechanisms to survive within the bone niche, including the secretion of leukotoxins such as Panton-Valentine leukocidin (PVL). PVL is a pore-forming toxin exhibiting selective human tropism for C5a receptors (C5aR1 and C5aR2) and CD45 on neutrophils, monocytes, and macrophages. PVL is an important virulence determinant in lung, skin and soft tissue infections...

Marginal zone (MZ) B cells bridge innate and adaptive immunity by sensing bloodborne antigens and producing rapid antibody and cytokine responses. CD55 is a membrane-bound complement regulator that interferes with complement activation, an important component of innate immunity. CD55 also regulates adaptive immunity-CD55 downregulation is critical for germinal center reactions. MZ B cells also express low CD55, but its role in MZ B cell function is unknown. Using germline knockout mice, we found that similar numbers of MZ B cells are initially established in 3-week-old CD55-deficient mice compared to wild-type (WT) mice...

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) has a poor prognosis and is highly metastatic. Our prior studies have demonstrated the critical role of axon guidance pathway genes in PDAC and the connection between neuronal development and the tumor microenvironment. A recent study newly identified 20 neuronal development genes [disks large homolog 2 ( DLG2 ), neuron-glial-related cell adhesion molecule ( NRCAM ), neurexin3 ( NRXN3 ), mitogen-activated protein kinase 10 ( MAPK10 ), platelet-derived growth factor D ( PDGFD ), protein kinase C epsilon ( PRKCE ), potassium calcium-activated channel subfamily M alpha 1 ( KCNMA1 ), polycystic kidney and hepatic disease 1 ( PKHD1 ), neural cell adhesion molecule 1 ( NCAM1 ), neuregulin-1 ( NRG1 ), zinc finger protein 667 ( ZNF667 ), cystic fibrosis transmembrane conductance regulator ( CFTR ), acyl-CoA medium-chain synthetase-3 ( ACSM3 ), complement 6 ( C6 ), protein tyrosine phosphatase receptor type M ( PTPRM ), hypoxia-inducible factor 1 alpha ( HIF1A ), adenylyl cyclase 5 ( ADCY5 ), adherens junctions-associated protein 1 ( AJAP1 ), neurobeachin ( NBEA ), sodium voltage-gated channel alpha subunit 9 ( SCN9A )] that are associated with perineural invasion and poor prognosis of PDAC...

In adult mammals, injured retinal ganglion cells (RGCs) fail to spontaneously regrow severed axons, resulting in permanent visual deficits. Robust axon growth, however, is observed after intra-ocular injection of particulate β-glucan isolated from yeast. Blood-borne myeloid cells rapidly respond to β-glucan, releasing numerous pro-regenerative factors. Unfortunately, the pro-regenerative effects are undermined by retinal damage inflicted by an overactive immune system. Here, we demonstrate that protection of the inflamed vasculature promotes immune-mediated RGC regeneration...

There is an unmet need for new therapeutic strategies that target alternative pathways to improve the prognosis of patients with pulmonary arterial hypertension (PAH). As immunity has been involved in the development and progression of vascular lesions in PAH, we review the potential contribution of B cells in its pathogenesis and evaluate the relevance of B cell-targeted therapies. Circulating B cell homeostasis is altered in PAH patients, with total B-cell lymphopenia, abnormal subset distribution (expansion of naïve and antibody-secreting cells, reduction of memory B cells) and chronic activation...

In terrestrial ecosystems, most plant species can form beneficial associations with arbuscular mycorrhizal (AM) fungi. Arbuscular mycorrhizal fungi benefit plant nutrient acquisition and enhance plant tolerance to drought. The high osmolarity glycerol 1 mitogen-activated protein kinase (HOG1-MAPK) cascade genes have been characterized in Rhizophagus irregularis. However, the upstream receptor of the HOG1-MAPK cascade remains to be investigated. We identify the receptor kinase RiSho1 from R. irregularis, containing four transmembrane domains and one Src homology 3 (SH3) domain, corresponding to the homologue of Saccharomyces cerevisiae...

Age-related macular degeneration (AMD) is a devastating eye disease that causes permanent vision loss in the central part of the retina, known as the macula. Patients with such severe visual loss face a reduced quality of life and are at a 1.5 times greater risk of death compared to the general population. Currently, there is no cure for or effective treatment for dry AMD. There are several mechanisms thought to underlie the disease, for example, ageing-associated chronic oxidative stress, mitochondrial damage, harmful protein aggregation and inflammation...

BACKGROUND: Current methods for evaluating efficacy of cosmetics have limitations because they cannot accurately measure changes in the dermis. Skin sampling using microneedles allows identification of skin-type biomarkers, monitoring treatment for skin inflammatory diseases, and evaluating efficacy of anti-aging and anti-pigmentation products. MATERIALS AND METHODS: Two studies were conducted: First, 20 participants received anti-aging treatment; second, 20 participants received anti-pigmentation treatment...