Complement receptor 3

BACKGROUND: Accumulating evidence underscores the pivotal role of heightened inflammation in the pathophysiology of stress-related diseases, but the underlying mechanisms remain elusive. The complement system, a key effector of the innate immune system, produces the C5-cleaved activation product C5a upon activation, initiating inflammatory responses through the canonical C5a receptor 1 (C5aR1). While C5aR1 is expressed in stress-responsive brain regions, its role in stress responsiveness remains unknown...

BACKGROUND: The resiliency of embryonic development to genetic and environmental perturbations has been long appreciated; however, little is known about the mechanisms underlying the robustness of developmental processes. Aberrations resulting in neonatal lethality are exemplified by congenital heart disease arising from defective morphogenesis of pharyngeal arch arteries (PAAs) and their derivatives. OBJECTIVE: To uncover mechanisms underlying the robustness of PAA morphogenesis...

In calendar year 2023, the United States Food and Drug Administration (US FDA) approved a total of 55 new molecular entities, of which 12 were in the class of therapeutic antibodies. Besides antibody protein drugs, the US FDA also approved another five non-antibody protein drugs, making the broader class of protein drugs about 31% of the total approved drugs. Among the 12 therapeutic antibodies approved by the US FDA, 8 were relatively standard IgG formats, 3 were bivalent, bispecific antibodies and 1 was a trivalent, bispecific antibody...

Escalation of ecological concern due to biodegradable plastics has attracted the attention of many contemporary researchers. This study searched to investigate the acute and sub-chronic toxicity of polylactic acid (PLA) and polybutyleneadipate-co-terephthalate (PLA-PBAT) bio-microplastics on 3-month-old zebrafish to elucidate their potential toxic mechanisms. Acute toxicity assessments revealed 96 h-LC50 value of 12.69 mg/L for PLA-PBAT. Sub-chronic exposure of over 21 days revealed deviations in critical behavioral patterns and physiological indicators...

BACKGROUND: Ketogenic foods limit digestible carbohydrates but contain high fat, and have antioxidant and anti-inflammatory effects as well as improving mitochondrial function. β-Hydroxybutyrate (BHB), 1 of the ketone bodies, reduces the proinflammatory NLR family pyrin domain containing 3 inflammasomes, as well as chemokines in cultures. OBJECTIVES: We assessed the immune-modulating effects of 2 low-carbohydrate (LoCHO) foods varying in protein and fat and compared their effects with a food replete with high-carbohydrate (HiCHO) in healthy canines...

Preeclampsia is a syndrome with multiple etiologies. The diagnosis can be made without proteinuria in the presence of dysfunction of at least 1 organ associated with hypertension. The common pathophysiological pathway includes endothelial cell activation, intravascular inflammation, and syncytiotrophoblast stress. There is evidence to support, among others, immunologic causes of preeclampsia. Unlike defense immunology, reproductive immunology is not based on immunologic recognition systems of self/non-self and missing-self but on immunotolerance and maternal-fetal cellular interactions...

Sorting maturing neurons into distinct layers is critical for brain development, with disruptions leading to neurological disorders and pediatric cancers. Lamination coordinates where, when, and how cells interact, facilitating events that direct migrating neurons to their destined positions within emerging neural networks and control the wiring of connections in functional circuits. While the role of adhesion molecule expression and presentation in driving adhesive recognition during neuronal migration along glial fibers is recognized, the mechanisms by which the spatial arrangement of these molecules on the cell surface dictates adhesive specificity and translates contact-based external cues into intracellular responses like polarization and cytoskeletal organization remain largely unexplored...

BACKGROUND: Mesenchymal stem cells (MSCs) modulated by various exogenous signals have been applied extensively in regenerative medicine research. Notably, nanosecond pulsed electric fields (nsPEFs), characterized by short duration and high strength, significantly influence cell phenotypes and regulate MSCs differentiation via multiple pathways. Consequently, we used transcriptomics to study changes in messenger RNA (mRNA), long noncoding RNA (lncRNA), microRNA (miRNA), and circular RNA expression during nsPEFs application...

Recent progress in glomerular immune complex and complement-mediated diseases have refined diagnostic categories and informed mechanistic understanding of disease development in pediatric patients. Herein, we discuss selected advances in 3 categories. First, membranous nephropathy antigens are increasingly utilized to characterize disease in pediatric patients and include phospholipase A2 receptor (PLA2R), Semaphorin 3B (Sema3B), neural epidermal growth factor-like 1 (NELL1), and protocadherin FAT1, as well as the lupus membranous-associated antigens exostosin 1/2 (EXT1/2), neural cell adhesion molecule 1 (NCAM1), and transforming growth factor beta receptor 3 (TGFBR3)...

Staphylococcus aureus is a significant bacterial pathogen in both community and hospital settings, and the escalation of antimicrobial-resistant strains is of immense global concern. Vaccination is an inviting long-term strategy to curb staphylococcal disease, but identification of an effective vaccine has proved to be challenging. Three well-characterized, ubiquitous, secreted immune evasion factors from the staphylococcal superantigen-like (SSL) protein family were selected for the development of a vaccine...

OBJECTIVE: Eculizumab and ravulizumab are complement protein C5 inhibitors, showing efficacy and tolerability for patients with anti-acetylcholine receptor-positive (AChR+) generalized myasthenia gravis (gMG) in phase 3 clinical trials and subsequent analyses. The purpose of the present study was to evaluate the clinical significance of eculizumab and switching to ravulizumab for refractory AChR+ gMG patients in the real-world experience. METHODS: Among the database of Japan MG registry survey 2021, we studied AChR+ gMG patients who received eculizumab...

Because the selective estrogen receptor modulator tamoxifen was shown to be retina-protective in the light damage and rd10 models of retinal degeneration, the purpose of this study was to test whether tamoxifen is retina-protective in a model where retinal pigment epithelium (RPE) toxicity appears to be the primary insult: the sodium iodate (NaIO3 ) model. C57Bl/6J mice were given oral tamoxifen (in the diet) or the same diet lacking tamoxifen, then given an intraperitoneal injection of NaIO3 at 25 mg/kg...

Porcine epidemic diarrhea virus (PEDV) causes severe diarrhea and high mortality in neonatal suckling piglets, leading to significant economic losses to the swine industry. Panax notoginseng saponins (PNS) are bioactive extracts derived from the P. notoginseng plant. In this study, we investigated the anti-PEDV effect of PNS by employing various methodologies to assess their impact on PEDV in Vero cells. Using a CCK-8 (Cell Counting Kit-8) assay, we found that PNS had no significant cytotoxicity below the concentration of 128 µg/mL in Vero cells...

INTRODUCTION: Chimeric antigen receptor (CAR) T-cell therapies are novel, potentially curative therapies for haematological malignancies. CAR T-cell therapies are associated with severe toxicities, meaning patients require monitoring during acute and postacute treatment phases. Electronic patient-reported outcomes (ePROs), self-reports of health status provided via online questionnaires, can complement clinician observation with potential to improve patient outcomes. This study will develop and evaluate feasibility of a new ePRO system for CAR-T patients in routine care...

INTRODUCTION: T follicular (TFH) and peripheral helper (TPH) cells have been increasingly recognized as a pathogenic subset of CD4 T cells in systemic lupus erythematosus (SLE). The SLAM Associated Protein (SAP) regulates TFH and TPH function by binding to the co-stimulatory signaling lymphocyte activation molecule family (SLAMF) receptors that mediate T cell - B cell interactions. SAP and SLAMF are critical for TPH-dependent B cell maturation into autoantibody-producing plasma cells that characterize SLE pathogenesis...

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...