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Lack of Fc-epsilon receptors on murine eosinophils: implications for the functional significance of elevated IgE and eosinophils in parasitic infections.

Chronic infection with Schistosoma mansoni induces in humans and mice a Th2-dominant immune response in which eosinophils and IgE are conspicuously elevated. Human eosinophils express IgE receptors that participate in an IgE-dependent eosinophil-mediated ADCC reaction against Schistosomula larvae in vitro. To investigate the expression of IgE receptors on murine eosinophils, they were purified (>95% pure by Giemsa-stained cytospin preparations) from liver granulomas of Schistosoma-infected mice. Flow cytometric analysis showed the absence of the low-affinity IgE receptor Fc-epsilon RII (CD23)

Single-cell RNA-seq reveals developmental plasticity with coexisting oncogenic states and immune evasion programs in ETP-ALL.

Lineage plasticity and stemness have been invoked as causes of therapy resistance in cancer, because these flexible states allow cancer cells to dedifferentiate and alter their dependencies. We investigated such resistance mechanisms in relapsed/refractory early T-cell progenitor acute lymphoblastic leukemia (ETP-ALL) carrying activating NOTCH1 mutations via full-length single-cell RNA sequencing (scRNA-seq) of malignant and microenvironmental cells. We identified 2 highly distinct stem-like states that critically differed with regard to cell cycle and oncogenic signaling. Fast-cycling stem-li

Sphingomyelin Synthase 2 Inhibition Ameliorates Cerebral Ischemic Reperfusion Injury Through Reducing the Recruitment of Toll-Like Receptor 4 to Lipid Rafts.

Background Inflammation is recognized as an important contributor of ischemia/reperfusion (I/R) damage after ischemic stroke. Sphingomyelin synthase 2 (SMS2), the key enzyme for the biosynthesis of sphingomyelin, can function as a critical mediator of inflammation. In the present study, we investigated the role of SMS2 in a mouse model of cerebral I/R. Methods and Results Cerebral I/R was induced by 60-minute transient middle cerebral artery occlusion in SMS2 knockout (SMS2-/-) mice and wild-type mice. Brain injury was determined by neurological deficits and infarct volume at 24 and 72 hours a

Interplay between monocyte subsets and leukemic blasts shapes the immune microenvironment and sustains minimal residual disease in pediatric B-cell acute lymphoblastic leukemia.

OBJECTIVE: Persistent minimal residual disease (MRD) significantly contributes to chemotherapy resistance and relapse in pediatric B-cell acute lymphoblastic leukemia (B-ALL), with conventional clinical risk factors insufficiently explaining the variability in patient prognoses. This study sought to explore potential mechanisms linked to sustained MRD by integrating analyses of clinical cohorts with single-cell transcriptomics, aiming to identify reliable biomarkers for risk stratification and targeted therapy. METHODS: Ninety-seven children with newly diagnosed B-ALL were enrolled and strati

Single-cell sequencing-based analysis of CD4 + T-cell and B-cell heterogeneity in patients with lupus nephritis.

OBJECTIVE: Systemic lupus erythematosus (SLE) is a prevalent chronic autoimmune disorder that can affect various organs and tissues throughout the body, with the kidneys being the most commonly involved, often leading to lupus nephritis (LN). Immune cells, notably CD4 + T cells and B cells, are crucial in the development of SLE. Investigating the heterogeneity of CD4 + T cells and B cells in patients with LN using single-cell technology is of significant importance. METHODS: With informed consent, this study explored the profiles of LN CD4 + T and B cells through single-cell transcriptome sequ

[Effects of Luhong Yixin Granules on myocardial fibrosis in heart failure rats based on TGF-β1/Smads signaling pathway].

To investigate the effects of Luhong Yixin Granules on myocardial fibrosis in rats with heart failure and its possible mechanism, a total of 60 male Wistar rats were randomly divided into the control group, model group, and low-, medium-and high-dose Luhong Yixin Granules groups, with 12 rats in each group. Except for those in the control group, rats in the other groups were induced by intraperitoneal injection of doxorubicin(DOX) into a rat model. After the Luhong Yixin Granules were dissolved in the same amount of normal saline, they were given by gavage at low, medium and high doses(2.8, 5.

Pectin: A Bioactive Food Polysaccharide with Cancer Preventive Potential.

Pectin is an acidic heteropolysaccharide found in the cell walls and the primary and middle lamella of land plants. To be authorized as a food additive, industrial pectins must meet strict guidelines set forth by the Food and Agricultural Organization and must contain at least 65% polygalacturonic acid to achieve the E440 level. Fruit pectin derived from oranges or apples is commonly used in the food industry to gel or thicken foods and to stabilize acid-based milk beverages. It is a naturally occurring component and can be ingested by dietary consumption of fruit and vegetables. Preventing lo

Antifibrotics in liver disease: are we getting closer to clinical use?

The process of wound healing in response to chronic liver injury leads to the development of liver fibrosis. Regardless of etiology, the profound impact of the degree of liver fibrosis on the prognosis of chronic liver diseases has been well demonstrated. While disease-specific therapy, such as treatments for viral hepatitis, has been shown to reverse liver fibrosis and cirrhosis in both clinical trials and real-life practice, subsets of patients do not demonstrate fibrosis regression. Moreover, where disease-specific therapies are not available, the need for antifibrotics exists. Increased un

Early Diagnosis of Herpes Zoster Neuralgia: A Narrative Review.

BACKGROUND: Early intervention reduces the incidence of postherpetic neuralgia (PHN). Typical shingles are easy to diagnose; however, there is no clear diagnostic method for neuralgia symptoms manifested before the onset of the rash, which can easily cause misdiagnosis. This not only increases the patient's pain, medical expenses, and mental burden, but more importantly, delays the valuable time for early treatment of shingles, and increases the probability of complications and PHN. OBJECTIVE: In this paper, the diagnostic methods of preherpetic neuralgia were summarized and analyzed, and the

AllergoOncology - the impact of allergy in oncology: EAACI position paper.

Th2 immunity and allergic immune surveillance play critical roles in host responses to pathogens, parasites and allergens. Numerous studies have reported significant links between Th2 responses and cancer, including insights into the functions of IgE antibodies and associated effector cells in both antitumour immune surveillance and therapy. The interdisciplinary field of AllergoOncology was given Task Force status by the European Academy of Allergy and Clinical Immunology in 2014. Affiliated expert groups focus on the interface between allergic responses and cancer, applied to immune surveill

Genetic testing and blood biomarkers in paediatric pulmonary hypertension. Expert consensus statement on the diagnosis and treatment of paediatric pulmonary hypertension. The European Paediatric Pulmonary Vascular Disease Network, endorsed by ISHLT and DGPK.

Childhood-onset pulmonary arterial hypertension (PAH) is considered complex and multifactorial, with relatively poor estimates of the natural history of the disease. Strategies allowing earlier detection, establishment of disease aetiology together with more accurate and sensitive biomarkers could enable better estimates of prognosis and individualise therapeutic strategies. Evidence is accumulating that genetic defects play an important role in the pathogenesis of idiopathic and hereditary forms of PAH. Altogether nine genes have been reported so far to be associated with childhood onset PAH

Effects of In Utero Exposure to Ethinyl Estradiol on Tamoxifen Resistance and Breast Cancer Recurrence in a Preclinical Model.

BACKGROUND: Responses to endocrine therapies vary among patients with estrogen receptor (ER+) breast cancer. We studied whether in utero exposure to endocrine-disrupting compounds might explain these variations. METHODS: We describe a novel ER+ breast cancer model to study de novo and acquired tamoxifen (TAM) resistance. Pregnant Sprague Dawley rats were exposed to 0 or 0.1 ppm ethinyl estradiol (EE2), and the response of 9,12-dimethylbenz[a]anthracene (DMBA)-induced mammary tumors to 15 mg/kg TAM, with (n = 17 tumors in the controls and n = 20 tumors in EE2 offspring) or without 1.2 g/kg val

The clinical application of angiostatic therapy in combination with radiotherapy: past, present, future.

Although monotherapy with angiostatic drugs is still far from effective, there is abundant evidence that angiostatic therapy can improve the efficacy of conventional treatments like radiotherapy. This has instigated numerous efforts to optimize and clinically implement the combination of angiostatic drugs with radiation treatment. The results from past and present clinical trials that explored this combination therapy indeed show encouraging results. However, current findings also show that the combination has variable efficacy and is associated with increased toxicity. This indicates that com

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… For example, our previous work has focussed on the role of galectins in tumor angiogenesis and cancer [ 35 – 40 ]. This was instigated by our discovery of galectin-1 as a pro-angiogenic factor that is essential for endothelial cell function during tumor angiogenesis [ 41 – 44 ]. … Schulkens IA Heusschen R van den Boogaart V van Suylen RJ Dingemans AM Griffioen AW Thijssen VL Galectin expression profiling identifies galectin-1 and galectin-9Δ5 as prognostic factors in stage I/II non-small cell lung cancer PLoS One 2014 9 e107988 25259711 10.1371/journal.pone.0107988 PMC4178059 …

TGF-β in hematologic malignancies: molecular functions and clinical applications.

Transforming growth factor-β (TGF-β) represents a family of multifunctional cytokines, primarily secreted by megakaryocytes, monocytes, T lymphocytes, bone marrow stromal cells, and other cell types. TGF-β plays an essential role in various physiological processes, including the regulation of cell proliferation, differentiation, apoptosis, and immune homeostasis. As a key immunoregulatory cytokine, TGF-β contributes to an immunosuppressive network within the microenvironment of hematologic malignancies by modulating the functions of both adaptive and innate immune cells. Current studies have s

NDP52 и его новая роль в патогенезе.

Автофагика - это процесс, способствующий выживанию, который регулирует деградацию и обновление клеточных компонентов, что делает его важнейшим механизмом для клеточного гомеостазиза. Существуют выборочные формы автофагии, характерные для ряда субстратов, таких, как патогены (бактерии или вирусы), белковые агрегаты или излишние/поврежденные органеллы. Эти процессы включают в себя в качестве ключевых игроков автофагичные рецепторы, которые связывают груз, подлежащий деградации, с автофагическим оборудованием. Среди них NDP52 (известный также как КАКПО2) был охарактеризован как «бридж» между авто

Frailty in Aging and the Search for the Optimal Biomarker: A Review.

In the context of accelerated aging of the population worldwide, frailty has emerged as one of the main risk factors that can lead to loss of self-sufficiency in older people. This syndrome is defined as a reduced state of physiological reserve and functional capacity. The main diagnostic tools for frailty are based on scales that show deficits compared to their clinical application, such as the Fried frailty phenotype, among others. In this context, it is important to have one or more biomarkers with clinical applicability that can objectively and precisely determine the degree or risk of fra

Role of Next Generation Immune Checkpoint Inhibitor (ICI) Therapy in Philadelphia Negative Classic Myeloproliferative Neoplasm (MPN): Review of the Literature.

The Philadelphia chromosome-negative (Ph-) myeloproliferative neoplasms (MPNs), which include essential thrombocythemia (ET), polycythemia vera (PV), and myelofibrosis (MF), are enduring and well-known conditions. These disorders are characterized by the abnormal growth of one or more hematopoietic cell lineages in the body's stem cells, leading to the enlargement of organs and the manifestation of constitutional symptoms. Numerous studies have provided evidence indicating that the pathogenesis of these diseases involves the dysregulation of the immune system and the presence of chronic inflam

Флюидные биомаркеры в демиелионирующих синдромах: прошлое, настоящее и перспективы.

По-прежнему продолжается работа над диагностическим алгоритмом демиелионирующих расстройств центральной нервной системы, а также поиск идеальных биомаркеров. Так называемый "идеальный" биомаркер должен обеспечивать точное различие между наиболее распространенными демиелионирующими патологиями ЦНС и подтипами одной и той же патологии (например, переход от релапсирующего многоразового склероза к вторичному прогрессивному фенотипу). Достижения в области технологии способствовали проведению этого исследования, и в нижеследующих разделах мы всесторонне проанализируем большинство из них, охарактериз

Novel diagnostic options for endometriosis - Based on the glycome and microbiome.

BackgroundEndometriosis is a chronic gynaecological disease whose aetiology is still unknown. Despite its prevalence among women of reproductive age, the pathology of the disease has not yet been elucidated and only symptomatic treatment is available. Endometriosis has high latency and diagnostic methods are both limited and invasive.Aim of reviewThe aim of this review is to summarise minimally invasive or non-invasive diagnostic methods for endometriosis and their diagnostic efficiencies. Furthermore, we discuss the identification and diagnostic potential of novel disease biomarkers of microb

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… Inflammatory proteins and cytokines Immunomodulatory factors, such as Galectin-1, Galectin-3 and Galectin-9 have been investigated, but most of them require more data to assess usability and some have already proven to be inadequate biomarker candidates for EMS [71] . … Galectins bind β-galactoside sugars and are involved in the regulation of apoptosis and they may play an indirect role in the abnormal survival of endometrial cells outside the uterus. …

Emerging Immunotherapy for Acute Myeloid Leukemia.

Several immune checkpoint molecules and immune targets in leukemic cells have been investigated. Recent studies have suggested the potential clinical benefits of immuno-oncology (IO) therapy against acute myeloid leukemia (AML), especially targeting CD33, CD123, and CLL-1, as well as immune checkpoint inhibitors (e.g., anti-PD (programmed cell death)-1 and anti-CTLA4 (cytotoxic T-lymphocyte-associated protein 4) antibodies) with or without conventional chemotherapy. Early-phase clinical trials of chimeric antigen receptor (CAR)-T or natural killer (NK) cells for relapsed/refractory AML showed