Результаты поиска

Identification and validation of biomarkers associated with cellular senescence and demethylation in acute myocardial infarction.

Acute myocardial infarction (AMI) triggered cardiomyocyte senescence and impaired cardiac function. Methylation modifications and related enzymes in patients were also significantly altered, but the association between cellular senescence and demethylation remained unclear. This study obtained data from public databases, screened candidate genes by intersecting differentially expressed genes (DEGs) with related genes, identified characteristic genes using three machine learning methods to determine biomarkers, and explored their regulatory mechanisms through gene set enrichment analysis (GSEA)

Markers of Type 2 Inflammation and Immunosenescence Are Upregulated in Localized Scleroderma.

Localized scleroderma (LS) is an autoimmune, fibrotic skin disease that is thought to be triggered by environmental factors. Recent evidence from systemic autoimmune diseases proposed that the induction of immunosenescence may link environmental triggers with autoimmunity development. We aimed to explore the inflammatory signature in juvenile LS and investigate the presence of DNA instability and immunosenescence using publicly available transcriptomic data. High-throughput RNA sequencing data from 28 juvenile LS and 10 healthy controls were analyzed. Unsupervised clustering, pathway analyses,

The single-cell immune landscape of HIV-associated aggressive B-cell lymphoma.

BACKGROUND: Human immunodeficiency virus (HIV)-associated lymphomas (HAL), mainly aggressive B-cell lymphomas, pose a significant challenge in cancer research due to their multifaceted pathogenesis and aggressive clinical course. Despite the clinical importance, the genomic and immune characteristics of these lymphomas remain poorly elucidated. METHODS: We employed single-cell RNA sequencing (scRNA-seq) on lymph node samples from aggressive B-cell lymphomas, mainly including 6 cases of diffuse large B-cell lymphoma (DLBCL) and 5 cases of Burkitt lymphoma (BL) from people living with HIV (PLWH

Adipose Dysfunction Caused by Obesity and Radiation Therapy Rewires the Prostate Stroma Toward Tumor Progression.

Obesity is associated with chronic adipose dysfunction characterized by oxidative stress, inflammation, senescence, and fibrosis, which can promote tumor progression. In prostate cancer, periprostatic adipose tissue may directly influence the prostate microenvironment. Radiation therapy is widely used in prostate cancer, but radiation-induced adipose dysfunction in obesity and its impact on the prostate microenvironment remain poorly understood. In the present study, we investigated the impact of obese and irradiated obese adipose microenvironments on prostate stromal remodeling, as well as th

A single-cell atlas characterizes dysregulation of the bone marrow immune microenvironment associated with outcomes in multiple myeloma.

Multiple myeloma (MM) remains incurable despite advances in treatment options. Although tumor subtypes and specific DNA abnormalities are linked to worse prognosis, the impact of immune dysfunction on disease emergence and/or treatment sensitivity remains unclear. We developed an Immune Atlas of MM by generating profiles of 1,397,272 single cells from the bone marrow (BM) of 337 newly diagnosed participants and characterized immune and hematopoietic cell populations. Cytogenetic risk-based analysis revealed heterogeneous associations with T cells of BM, with 17p13 deletion showing distinct enr

Elevated IL-15 levels in systemic lupus erythematosus: potential pathogenesis insight and therapeutic target.

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease characterized by persistent immune cell activation and the overproduction of autoantibodies, affecting various organs such as joints, kidneys, and skin. Interleukin-15 (IL-15) is a pleiotropic cytokine that modulates immune cells of the innate and adaptive immune systems, playing a crucial role in the development of inflammatory and protective immune responses. However, the role of IL-15 in SLE pathogenesis and the therapeutic effects of IL-15 blockade on SLE remain unknown. In this study, we conducted flow cytometry analysis a

Identification of biomarkers for pediatric sepsis based on machine learning and bioinformatics analysis.

Pediatric sepsis is a systemic inflammatory syndrome caused by dysregulated host immune responses, with a high mortality rate and a lack of effective biomarkers, posing significant challenges for early diagnosis and treatment. This study integrated six bulk RNA-seq datasets related to pediatric sepsis, including 497 patients and 116 healthy control samples. Weighted gene co-expression network analysis was used to identify gene modules significantly associated with pediatric sepsis, and 237 high-confidence biomarkers were screened based on 14 machine learning models, among which RORA and GPR183

Миэлоидно-подавительские клетки в карциноме ларингеальных клеток: недостаточно изученная иммунодепрессивная ось и стратегическая цель преодоления ингибиторного сопротивления на контрольно-пропускных пунктах.

Углубленные клеточные карциномы (LSCC) указывают на неизменно низкий коэффициент объективной реакции на ингибиторы на контрольно-пропускных пунктах (ИКИ) в отношении запрограммированных death-1 (В тыс.PD-1Путь. Его иммуновосприимчивая опухоль (TME), обогащенная макрофагами, связанными с опухолью, иммунодепрессивными опухолью, связанными с нейтрофилами (TANs), и регуляционными Т клетками, является основным фактором отказа ICI. Пока что one Миелоидное население, имеющее центральное значение для сопротивления ИКИ во многих случаях, не получает особого внимания в связи с этим заболеванием. Миелиои

Longevity through immunity: the unusual naked mole-rat immune system.

Naked mole-rats (NMR, Heterocephalus glaber) defy Gompertzian rules of mortality and age-dependent senescence to lead healthy lives well into their fourth decade. The NMR immune system likely contributes to this phenotype by protecting against infections, regulating tissue repair, and eradicating neoplastic cells. In keeping with their many other paedomorphic traits, adult NMRs retain functional thymic tissue in the submandibular triangle. Despite this additional thymic tissue, perinatal NMR thymi are half the size of mouse thymi, yet both species show similar thymic involution trajectories. S

Impact of aging on the pathophysiology of dry eye disease: A systematic review and meta-analysis.

PURPOSE: Dry eye disease (DED) is a common age-related ocular surface disease. However, it is unknown how aging influences the ocular surface microenvironment. This systematic review aims to investigate how the aging process changes the ocular surface microenvironment and impacts the development of DED. METHODS: An article search was performed in PubMed, EMBASE, and Web of Science. 44 studies reporting on age-related ocular changes and 14 large epidemiological studies involving the prevalence of DED were identified. 8 out of 14 epidemiological studies were further analyzed with meta-analysis.

Human Regulatory T Cells From Umbilical Cord Blood Display Increased Repertoire Diversity and Lineage Stability Relative to Adult Peripheral Blood.

The human T lymphocyte compartment is highly dynamic over the course of a lifetime. Of the many changes, perhaps most notable is the transition from a predominantly naïve T cell state at birth to the acquisition of antigen-experienced memory and effector subsets following environmental exposures. These phenotypic changes, including the induction of T cell exhaustion and senescence, have the potential to negatively impact efficacy of adoptive T cell therapies (ACT). When considering ACT with CD4+CD25+CD127-/lo regulatory T cells (Tregs) for the induction of immune tolerance, we previously repor

Circulating T Cells and Cardiovascular Risk in People With and Without HIV Infection.

BACKGROUND: Lower CD4+ cell count in people with HIV infection (PWH) is associated with increased cardiovascular disease (CVD) risk. Whether subsets of CD4+ T helper cells are linked with CVD is unclear. OBJECTIVES: The aim of this study was to explore the association between peripherally circulating CD4+ T cell subsets and incident CVD. METHODS: Data from 1,860 participants (1,270 PWH) without prevalent CVD from the VACS (Veterans Aging Cohort Study), a prospective, observational cohort of veterans with and without HIV infection, were analyzed. T cell subsets were quantified in baseline sam

Acute COVID-19 is associated with altered CD8 T-cells indicative of impaired ability to control Epstein-Barr virus reactivation.

Increasing evidence suggests that reactivation of latent EBV in patients with COVID-19 may be linked to the development of post-acute sequelae of COVID-19, colloquially known as Long COVID. However, the reason for this co-occurrence of primary infection and reactivation of latent viruses remains elusive. During the first wave of COVID-19, we assessed all major immune cell populations by flow cytometry in a cohort of 61 patients with moderate to critical COVID-19 at the time of hospitalization. Additional blood samples from these patients were biobanked for later analysis. Using these biobanked

Aging and immune response in chronic human schistosomiasis.

There has been no systematic study of the immune response of individuals over 60 residing in areas endemic for Schistosoma mansoni infection although senescence is reportedly associated with susceptibility to infection and progressive decline in immune function. We have shown previously, in two endemic areas in Minas Gerais, Brazil, that the frequency of individuals over 60 with chronic schistosomiasis is no longer negligible. Several aging-related immunological alterations are already described in medical literature, mostly in the T-cell compartment. Since aging is associated with a decline i

Сверхклеточная везикла в качестве главных регуляторов иммунной модуляции в Мультимиломе.

Множественная миелома (ММ) — генетически и клинически разнородная плазменная порча клеток, характеризующаяся клональным расширением различных клеток В внутри костного мозга (БМ). Пациенты начинают с моноклональной гаммопатии неизвестного значения (MMUS) и переходят на промежуточную стадию под названием Smouldering multieloma (SMM), характеризующуюся несколькими генетическими изменениями, представляющими геномную основу злокачественного клона. Проходы на контрольно-пропускных пунктах иммунной системы играют ключевую роль в формировании иммуноподавляющей ниши BM, что способствует дисфункции Т-кл

Совпадение в полном тексте источника
… T-cell senescence represents another mechanism contributing to immune dysfunction in MM and has distinct features. For example, senescent T-cell subsets appear to develop independently of telomere shortening. …

Association of Monocyte Migration Marker CD11b With Pulmonary Function in People Living With HIV.

BACKGROUND: Maladaptive immune responses contribute to the pathogenesis of many chronic lung diseases. Here, we tested hypotheses that CD4 and CD8 T-cell and monocyte phenotypes are associated with lung function in people living with HIV and those without HIV. METHODS: Markers of T cell differentiation, activation, exhaustion and senescence, and markers of monocyte recruitment and migration were quantified in 142 HIV-positive and 73 HIV-negative participants of the Pittsburgh HIV Lung Cohort. All participants underwent lung function testing. RESULTS: CD4 or CD8 T-cell phenotypes were not ass

C-reactive protein impairs immune response of CD8+ T cells via FcγRIIb-p38MAPK-ROS axis in multiple myeloma.

BACKGROUND: C-reactive protein (CRP) is a prototypical acute phase protein in humans with the function of regulating immune cells. Serum CRP levels are elevated in multiple myeloma (MM), associated with MM cell proliferation and bone destruction. However, its direct effects on T lymphocytes in MM have not been elucidated. METHODS: Public data sets were used to explore the correlation of CRP levels with immune cell infiltration and cytotoxicity score of CD8+ T cells in MM. In vitro, repeated freeze-thaw myeloma cell lines were taken as tumor antigens to load dendritic cells (DCs) derived from

Aging associated immunosenescence in rheumatoid arthritis identified by machine learning and single cell profiling.

Rheumatoid arthritis (RA) is increasingly prevalent among older adults, who often experience more severe symptoms and face significant treatment challenges. This study aims to identify specific genes associated with aging in RA and to analyze their immune infiltration using machine learning techniques. We sourced senescent genes from the HARG database and utilized three RA patient datasets obtained from the GEO database. Differential analysis revealed 50 age-related differentially expressed genes (ARDEGs) that intersected with senescent genes. Hub genes were identified through protein-protein

Mucosal Immune Responses in People Living with HIV May Confer Protection from SARS-CoV-2 Infections After COVID-19 Vaccination.

Background/Objectives: The induction of anti-SARS-CoV-2 antibodies by COVID-19 vaccination reduces morbidity and mortality, but immune responses may be compromised in people living with HIV (PLWH). The aims of the current study were to determine whether viral suppression (VS) or immune reconstitution (IR) in PLWH directly affected their ability to produce effective levels of anti-SARS-CoV-2 antibodies in mucosal secretions or blood induced by vaccination. Methods: Anti-SARS-CoV-2 spike IgG, IgA and secretory IgA (SIgA) antibodies and their avidities were measured by ELISA in HIV-negative healt

HIV-infected individuals with low CD4/CD8 ratio despite effective antiretroviral therapy exhibit altered T cell subsets, heightened CD8+ T cell activation, and increased risk of non-AIDS morbidity and mortality.

A low CD4/CD8 ratio in elderly HIV-uninfected adults is associated with increased morbidity and mortality. A subset of HIV-infected adults receiving effective antiretroviral therapy (ART) fails to normalize this ratio, even after they achieve normal CD4+ T cell counts. The immunologic and clinical characteristics of this clinical phenotype remain undefined. Using data from four distinct clinical cohorts and three clinical trials, we show that a low CD4/CD8 ratio in HIV-infected adults during otherwise effective ART (after CD4 count recovery above 500 cells/mm3) is associated with a number of i