Immune mechanics

Triatomines (kissing bugs) and tsetse flies (genus: Glossina) are natural vectors of Trypanosoma cruzi and Trypanosoma brucei, respectively. T. cruzi is the causative agent of Chagas disease, endemic in Latin America, while T. brucei causes African sleeping sickness disease in sub-Saharan Africa. Both triatomines and tsetse flies are host to a diverse community of gut microbiota that co-exist with the parasites in the gut. Evidence has shown that the gut microbiota of both vectors plays a key role in parasite development and transmission...

Designing and developing photosensitizers with cell membrane specificity is crucial for achieving effective multimodal therapy of tumors compared to other organelles. Here, we designed and screened a photosensitizer CM34 through donor/receptor regulation strategies, and it is able to achieve long-retention cell membrane targeting. It is not only an extremely excellent cell membrane targeted tumor theranostic agent, but also found to be a promising potential immune activator. Specifically, CM34 with a larger intramolecular twist angle is more likely to form larger aggregates in aqueous solutions, and the introduction of cyanide group also enhances its interaction with cell membranes, which were key factors hindering molecular penetration of the cell membrane and prolonging its residence time on the cell membrane, providing conditions for further membrane targeted photodynamic therapy...

Acute invasive fungal sinusitis (AIFS) classically presents as an aggressive fungal infection that can spread beyond its origin in the sinuses in immunocompromised patients. Although there have been reports of AIFS in immunocompetent, non-diabetic patients, it is extremely rare and the true mechanism behind it is unknown. A thirty-eight year old immunocompetent, non-diabetic woman underwent bilateral ESS for chronic rhinosinusitis with nasal polyps at a tertiary care center and post-operatively developed AIFS...

The co-occurrence of myasthenia gravis (MG) and paroxysmal nocturnal hemoglobinuria (PNH) is rare; only one case has been published so far. We report a 63-year-old Caucasian female patient who was diagnosed with MG at the age of 43. Thymoma was also detected, and so it was surgically resected, which resulted in reasonable disease control for nearly 20 years. Slight hemolysis began to emerge, and then myasthenia symptoms progressed, so immunosuppressive therapy was started. Due to progressive disease and respiratory failure, the patient underwent plasmapheresis, and ventilatory support was stopped...

Islet autoantibodies predict type 1 diabetes (T1D) but can be transient in murine and human T1D and are not thought to be directly pathogenic. Rather, these autoantibodies signal B cell activity as antigen-presenting cells (APCs) that present islet autoantigen to diabetogenic T cells to promote T1D pathogenesis. Disrupting B cell APC function prevents T1D in mouse models and has shown promise in clinical trials. Autoantigen-specific B cells thus hold potential as sophisticated T1D biomarkers and therapeutic targets...

BACKGROUND: One of the mechanisms regulating the biological activity of tumor necrosis factor (TNF) in cells is the co-expression of TNFR1/TNFR2 receptors. A model with a differential level of receptor expression is required to evaluate the contribution of these mechanisms. AIM: The development of a cellular model to compare the effects of TNF on cells depending on the presence of both receptors and TNFR2 alone. METHODS: TNFR1 absence modifications of ZR-75/1 and K-562 cell lines were obtained by TNFR1 knockout...

Sea surface temperatures are rising at unprecedented rates, leading to a progressive degradation of complex habitats formed by coral reefs. In parallel, acute thermal stress can lead to physiological challenges for ectotherms that inhabit coral reefs, including fishes. Warming and habitat simplification could push marine fishes beyond their physiological limits in the near future. Specifically, questions remain on how warming and habitat structure influence the brain of marine fishes. Here we evaluated how thermal stress and habitat loss are acting independently and synergistically as stressors in a damselfish of the Western Atlantic, Abudefduf saxatilis...

Cancer drug testing in animals is an extremely poor predictor of the drug's safety and efficacy observed in humans. Hence there is a pressing need for functional testing platforms that better predict traditional and immunotherapy responses in human, live tumor tissue or tissue constructs, and at the same time are compatible with the use of mouse tumor tissue to facilitate building more accurate disease models. Since many cancer drug actions rely on mechanisms that depend on the tumor microenvironment (TME), such platforms should also retain as much of the native TME as possible...

BACKGROUND: An increasing corpus of evidence has identified the involvement of N-acetyltransferase 1 (NAT1), a member of the NAT family, in the progression of various cancers. However, the specific function of NAT1 in colon cancer (COAD) remains elusive. This study aims to decip her the role of NAT1 in COAD and its associated mechanisms. METHODS: The Tumor Immunity Evaluation Resource (TIMER), The Cancer Genome Atlas (TCGA), and the Gene Expression Omnibus (GEO) databases were employed to assess the NAT1 expression level in COAD...

INTRODUCTION: Non-small cell lung cancer (NSCLC) is a prevalent respiratory system tumor. Triggered transposable element derivative 1 (TIGD1) exhibits significant overexpression in various tumor cells and tissues, suggesting its involvement in cancer progression. METHODS: Clinical data and gene expression profiles of lung adenocarcinoma were collected from TCGA, UCSC XENA, and GEO databases. Computational techniques and empirical studies were employed to analyze the role of TIGD1 in NSCLC...

BACKGROUND: Up to 20% of people with HIV (PWH) fail to recover their CD4+ T cell counts to levels similar to healthy controls after suppressive antiretroviral therapy (ART). Immune non-responders (INRs) are PWH on suppressive ART with CD4+ T cell counts lower than 350 cells/mL, whereas their CD8+ T cell counts are higher than healthy controls. We are the first group to report that increased anti-CD4 autoantibody IgGs in INRs are responsible for blunted CD4+ T cell reconstitution in PWH with ART and viral suppression through anti-CD4 IgG-induced antibody-mediated cytotoxicity (ADCC) against CD4+ T cells in vitro ...

INTRODUCTION: The culture of Pacific oysters ( Crassostrea gigas ) is of significant socio-economic importance in the U.S. Pacific Northwest and other temperate regions worldwide, with disease outbreaks acting as significant bottlenecks to the successful production of healthy seed larvae. Therefore, the current study aims to describe the mechanisms of a probiotic combination in improving the survival of C. gigas larvae. Specifically, we investigate changes in C. gigas larval gene expression in response to V...

BACKGROUND: Despite therapy advances, one of the leading causes of cancer deaths still remains lung cancer. To improve current treatments or prevent non-small cell lung cancer (NSCLC), the role of the nutrition in cancer onset and progression needs to be understood in more detail. While in colorectal cancer, the influence of local microbiota derived SCFAs have been well investigated, the influence of SCFA on lung cancer cells via peripheral blood immune system should be investigated more deeply...

Interactions between macrophages and adipocytes in adipose tissue are critical for the regulation of energy metabolism and obesity. Macrophage polarization induced by cold or other stimulations can drive metabolic reprogramming of adipocytes, browning, and thermogenesis. Accordingly, investigating the roles of macrophages and adipocytes in the maintenance of energy homeostasis is critical for the development of novel therapeutic approaches specifically targeting macrophages in metabolic disorders such as obesity...

INTRODUCTION: Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) presents substantial challenges in patient care due to its intricate multisystem nature, comorbidities, and global prevalence. The heterogeneity among patient populations, coupled with the absence of FDA-approved diagnostics and therapeutics, further complicates research into disease etiology and patient managment. Integrating longitudinal multi-omics data with clinical, health,textual, pharmaceutical, and nutraceutical data offers a promising avenue to address these complexities, aiding in the identification of underlying causes and providing insights into effective therapeutics and diagnostic strategies...

INTRODUCTION: Macrophages are an important component of innate immunity and involved in the immune regulation of multiple diseases. The functional diversity and plasticity make macrophages to exhibit different polarization phenotypes after different stimuli. During tumor progression, the M2-like polarized tumor-associated macrophages (TAMs) promote tumor progression by assisting immune escape, facilitating tumor cell metastasis, and switching tumor angiogenesis. Our previous studies demonstrated that functional remodeling of TAMs through engineered-modifying or gene-editing provides the potential immunotherapy for tumor...

BACKGROUND: Migraine has an increased prevalence in several immune disorders, but genetic cause-effect relationships remain unclear. Mendelian randomization (MR) was used in this study to explore whether immune diseases are causally associated with migraine and its subtypes. METHODS: We conducted a two-sample bidirectional multivariate Mendelian randomization study. Single-nucleotide polymorphisms (SNP) for six immune diseases, including rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), type 1 diabetes mellitus (T1D), allergic rhinitis (AR), asthma and psoriasis, were used as genetic instrumental variables...

The biosynthesis of C-reactive protein (CRP) in the liver is increased in inflammatory diseases including rheumatoid arthritis. Previously published data suggest a protective function of CRP in arthritis; however, the mechanism of action of CRP remains undefined. The aim of this study was to evaluate the effects of human CRP on the development of collagen-induced arthritis (CIA) in mice which is an animal model of autoimmune inflammatory arthritis. Two CRP species were employed: wild-type CRP which binds to aggregated IgG at acidic pH and a CRP mutant which binds to aggregated IgG at physiological pH...

INTRODUCTION: The gut microbiota, T cell subsets, and cytokines participate in tuberculosis (TB) pathogenesis. To date, the mechanisms by which these factors interactively promote TB development at different time points remain largely unclear. In the context of this study, We looked into the microorganisms in the digestive tract, T cell types, and cytokines related to tuberculosis. METHODS: According to QIIME2, we analyzed 16SrDNA sequencing of the gut microbiome on the Illumina MiSeq...

BACKGROUND: Malaria remains a major global health priority, and monoclonal antibodies (mAbs) are emerging as potential new tools to support efforts to control the disease. Recent data suggest that Fc-dependent mechanisms of immunity are important mediators of protection against the blood stages of the infection, but few studies have investigated this in the context of mAbs. We aimed to isolate mAbs agnostic to cognate antigens that target whole merozoites and simultaneously induce potent neutrophil activity measured by the level of reactive oxygen species (ROS) production using an antibody-dependent respiratory burst (ADRB) assay...