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Dietary magnesium restriction affects hematopoiesis and triggers neutrophilia by increasing STAT-3 expression and G-CSF production.

BACKGROUND & AIMS: Magnesium (Mg2+) is able to modulate the differentiation and proliferation of cells. Mg2+ restriction can trigger neutrophilia, but the processes that result in this change have yet to be investigated and are not fully understood. Hematopoiesis is a complex process that is regulated by many factors, including cytokines and growth factors, and is strongly influenced by nutrient availability. In this context, our objective was to investigate the impact of the short-term restriction of dietary Mg2+ on bone marrow hematopoietic and peripheral blood cells, especially in processes

Association of SCART1+ T cells with neutrophils and cytokine-mediated induction of immunosuppressive neutrophils in neuroblastoma.

Neuroblastoma (NB) is a pediatric solid tumor with poor outcomes in high-risk cases, largely driven by the tumor microenvironment (TME). Tumor-associated neutrophils (TANs) exert potent regulatory effects within the TME, but the mechanisms orchestrating their activation and functional polarization in NB remain elusive. Here, utilizing proteomic and single-cell transcriptomic analyses, we identify a distinct tumor-enriched SCART1+ T cell subset within the NB TME. This population prominently secretes IL-17A, GM-CSF, IL-22, and TNF-α. Moreover, the abundance of SCART1+ T cells correlates positive

CSF3R T618I, SETBP1 G870S, SRSF2 P95H, and ASXL1 Q780* tetramutation co-contribute to myeloblast transformation in a chronic neutrophilic leukemia.

Chronic neutrophilic leukemia (CNL) is a rare but serious myeloid malignancy. In a review of reported cases for WHO-defined CNL, CSF3R mutation is found in about 90% cases and confirmed as the molecular basis of CNL. Concurrent mutations are observed in CSF3R-mutated CNL patients, including ASXL1, SETBP1, SRSF2, JAK2, CALR, TET2, NRAS, U2AF1, and CBL. Both ASXL1 and SETBP1 mutations in CNL have been associated with a poor prognosis, whereas, SRSF2 mutation was undetermined. Our patient was a 77-year-old man and had no significant past medical history and symptoms with leukocytosis. Bone marrow

Neuroprotective peptides influence cytokine and chemokine alterations in a model of fetal alcohol syndrome.

OBJECTIVE: Fetal alcohol syndrome (FAS) is associated with intellectual disability and neurodevelopmental abnormalities. Neuroprotective pep … KC (both P < .003), similar to the controls. Alcohol exposure resulted in a significant increase of granulocyte colony-stimulating factor (G-CSF) (P < .003) as compared with controls, and treatment with NAP plus SAL prevented the alcohol-induced increase. IL-13 and IL-1β were decreased 6 hours after alcohol exposure, and exposure to alcohol plus NAP plus SAL did not completely amelior …

Adult respiratory distress syndrome-like disorders after allogeneic bone marrow transplantation.

BACKGROUND: Adult respiratory distress syndrome-like respiratory disorders are a serious, but uncommon, complication of bone marrow transplantation. METHODS: We measured various cytokines in 2 patients with respiratory disorders and 11 patients without respiratory problems after allogeneic bone marrow transplantation. RESULTS: The patients with respiratory disorders had elevated levels of interferon-gamma and interleukin-2 in the aplastic phase, and elevation of tumor necrosis factor-alpha, intercellular adhesion molecule-1, and interleukin-8 at the time of leukocyte recovery. Both patients

Transcriptomic analysis identifies candidate molecular mechanisms underlying SCF+G-CSF-reduced neuropathology in aged APP/PS1 mice.

BACKGROUND: Alzheimer's Disease (AD) is a neurodegenerative disease characterized by amyloid plaque deposition, tau hyperphosphorylation, neuroinflammation, and cognitive decline. Our previous studies demonstrated that combined treatment with stem cell factor (SCF) and granulocyte colony-stimulating factor (G-CSF) reduces AD pathology in APP/PS1 mice. The present study aimed to explore the molecular mechanisms underlying the effects of SCF+G-CSF using transcriptomic analysis. METHODS: Aged APP/PS1 mice received daily subcutaneous injections of SCF+G-CSF or vehicle for 12 days. RNA was extract…

Cytokine release syndrome in solid tumours: mechanism-based therapeutic strategies for prevention and management.

Cytokine release syndrome (CRS) represents a spectrum of immune hyperactivation initiated by rapid T-cell engagement and amplified through innate immune cells, particularly monocytes and macrophages, with downstream cytokine cascades driving endothelial dysfunction, capillary leak and organ impairment. CRS is a frequent, class-associated toxicity of T-cell-engaging immunotherapies and is being observed with increasing regularity as T-cell-redirecting therapies progress through clinical development in solid tumours. Although CRS is typically less severe in patients with solid tumours relative t

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… Subcutaneous administration is being explored as a means of attenuating systemic cytokine peaks and reducing CRS incidence. 56 Conversely, the use of granulocyte colony-stimulating factor (G-CSF) following lymphodepleting chemotherapy has been associated with an increased risk of severe CRS. 59 Accordingly …

CD55-expressing myeloid-derived suppressor cells (MDSCs) drive cancer immunoevasion.

BACKGROUND: Myeloid-derived suppressor cells (MDSCs) play a pivotal role in shaping the immunosuppressive tumor microenvironment, thereby driving tumor progression and contributing to resistance to therapy. The surface molecules expressed on MDSCs serve not only as identification markers but also as critical regulators of their immunosuppressive functions. Identifying surface markers that are both widely expressed and functionally significant on MDSCs is essential for the development of effective immunomodulatory therapies. METHODS: A comprehensive analysis of publicly available single-cell R

Akkermansia muciniphila reduces neuroinflammation and Aβ deposition via tryptophan metabolism in the APP/PS1 mouse model of Alzheimer's disease.

Akkermansia muciniphila (A. muciniphila), a beneficial gut bacterium, has increasingly attracted interests in Alzheimer's disease (AD) research, its specific role in the microbiota-gut-brain axis still remains unclear. In this study, we demonstrated that A. muciniphila administration improve cognitive deficits and reduce amyloid-beta (Aβ) deposition in APP/PS1 mice, a transgenic model of AD. Subsequently, it is revealed that A. muciniphila administration significantly alters gut microbiota diversity and composition. Mechanically, our metabolomics analysis of cecal contents indicates A. mucinip

Irritable Bowel Syndrome-like Symptoms in Patients With Ulcerative Colitis in Remission as Compared to Irritable Bowel Syndrome: Symptom Severity and Inflammatory Markers.

BACKGROUND/AIMS: Patients with ulcerative colitis in remission (UC-R) may experience symptoms consistent with irritable bowel syndrome (IBS). This prospective study aims to examine the relative influence of peripheral factors, such as gut mucosal inflammation, and central factors, like psychological conditions, on the severity of IBS symptoms to evaluates (1) the IBS Symptom Severity Score (IBS-SSS), (2) levels of inflammatory markers, and (3) the presence of psychological comorbidities across 3 groups: UC patients with IBS symptoms (UC-IBS), UC-R patients without IBS, and individuals with usu

A novel antioxidant and anti-inflammatory carboxymethylcellulose/chitosan hydrogel loaded with cannabidiol promotes the healing of radiation-combined wound skin injury in the 60Co γ-irradiated mice.

BACKGROUND: Combined radiation and wound skin injury (RW) are frequently observed in patients undergoing tumor surgery plus radiotherapy, and but specific treatment is lacking. Chitosan (CS) and carboxymethyl cellulose (CMC) are commonly used to prepare hydrogel with good biocompatibility and low toxicity. Cannabidiol (CBD) has presented anti-inflammatory, antioxidant, and neuroprotective properties. METHODS: CMC, CS, and CBD were used and designed for three types of hydrogels (CMC/CS2/CBD, CMC/CS3/CBD, CMC/CS4/CBD) with different ratios of CMC and CS based on previous report and our prelimin

Renal denervation achieves its antiarrhythmic effect through attenuating macrophage activation and neuroinflammation in stellate ganglia in chronic heart failure.

AIMS: Renal denervation (RDN) is widely investigated in multiple studies of sympathetically driven cardiovascular diseases. While the therapeutic potential of RDN for ventricular arrhythmia has been reported, the mechanisms responsible for its antiarrhythmic effect are poorly understood. Our recent study showed that macrophage expansion-induced neuroinflammation in the stellate ganglion (SG) was a critical factor for cardiac sympathetic overactivation and ventricular arrhythmogenesis in chronic heart failure (CHF). This study investigates if and how RDN decreases ventricular arrhythmias by att

Pro- and anti-inflammatory cytokines mediate the progression of severe anemia in malaria-infected children: A prospective study.

BACKGROUND: Severe Plasmodium falciparum malarial anemia is still the principal cause of death in children in underdeveloped countries. An imbalance between proinflammatory and anti-inflammatory cytokines is associated with malaria progression. This study evaluated circulating levels of selected inflammatory cytokines among malaria-infected children in Ghana. METHODS: This case-control study was conducted at Tamale Teaching Hospital, Ghana. One hundred and twenty children with malaria and 60 controls, aged 12-144 months were selected from April to July, 2023 for the study. Malaria was diagnos

Boost of innate immunity cytokines as biomarkers of response to extracorporeal photopheresis in patients with leukaemic cutaneous T-cell lymphoma.

BACKGROUND: Extracorporeal photopheresis (ECP) has emerged as a systemic first-line immunomodulatory therapy in leukaemic cutaneous T-cell lymphoma (L-CTCL) and is now beginning to be utilized in other T-cell-mediated diseases. Although ECP has been used for nearly 30 years, its mechanisms of action are not sufficiently understood, and biomarkers for response are scarce. OBJECTIVES: We aimed to investigate the immunomodulatory effects of ECP on cytokine secretion patterns in patients with L-CTCL, to help elucidate its mechanism of action. METHODS: A total of 25 patients with L-CTCL and 15 he

A Novel Quadruple Gene-Deleted BoHV-1-Vectored RVFV Subunit Vaccine Induces Humoral and Cell-Mediated Immune Response against Rift Valley Fever in Calves.

Rift Valley fever virus (RVFV) is considered to be a high biodefense priority based on its threat to livestock and its ability to cause human hemorrhagic fever. RVFV-infected livestock are also a significant risk factor for human infection by direct contact with contaminated blood, tissues, and aborted fetal materials. Therefore, livestock vaccination in the affected regions has the direct dual benefit and one-health approach of protecting the lives of millions of animals and eliminating the risk of severe and sometimes lethal human Rift Valley fever (RVF) disease. Recently, we have developed

Antenatal maternal depression, early life inflammation and neurodevelopment in a South African birth cohort.

BACKGROUND: Antenatal exposure to maternal psychological adversity, including depression, increases the risk of impaired neurodevelopment in children. The underlying biological mechanisms remain unclear, especially in early life during critical windows of development and maturation. This study investigated the association of antenatal maternal depression, maternal and early life inflammatory markers and neurodevelopmental outcomes in children at 2 years of age. METHODS: A subgroup of mothers and their children (n = 255) that were enrolled in a South African birth cohort study, the Drakenstein

GM-CSF perturbs cell identity in mouse pre-implantation embryos.

Growth factors became attractive candidates for medium supplementation to further improve the quality of embryo culture and to mimic in vivo nutrition. Granulocyte macrophage colony-stimulating factor (GM-CSF) is a cytokine influencing the maternal-fetal interface and supporting placental development in mouse and human. It is expressed in epithelial cells of the endometrium under the regulation of estrogens. The factor is already in clinical use and a large clinical trial showed that, if supplemented to an embryo culture medium, it leads to increased survival of embryos, especially in women wi

Isolation, Culture, and Genetic Engineering of Mammalian Primary Pigment Epithelial Cells for Non-Viral Gene Therapy.

Age-related macular degeneration (AMD) is the most frequent cause of blindness in patients >60 years, affecting ~30 million people worldwide. AMD is a multifactorial disease influenced by environmental and genetic factors, which lead to functional impairment of the retina due to retinal pigment epithelial (RPE) cell degeneration followed by photoreceptor degradation. An ideal treatment would include the transplantation of healthy RPE cells secreting neuroprotective factors to prevent RPE cell death and photoreceptor degeneration. Due to the functional and genetic similarities and the possibili

Clinical efficacy and safety of mecapegfilgrastim in small cell lung cancer as primary prophylaxis of neutropenia post chemotherapy: a retrospective analysis.

BACKGROUND: Neutropenia is the most common adverse reaction seen in small cell lung cancer after chemotherapy. Febrile neutropenia (FN) leads to an increase in hospitalizations and may even be life-threatening. This paper aims to investigate the efficacy and adverse reactions of mecapegfilgrastim in the primary prophylaxis of neutropenia in patients with small cell lung cancer after receiving intermediate risk chemotherapy with at least one patient risk factor. METHODS: The clinical records of 106 patients with small cell lung cancer admitted to Zhejiang Cancer Hospital from June 2019 to Janu