Critical ilness

SYNTAXIN-11 (STX11) is a SNARE protein that mediates the fusion of cytotoxic granules with the plasma membrane at the immunological synapses of CD8 T or NK cells. Autosomal recessive inheritance of deleterious STX11 variants impairs cytotoxic granule exocytosis, causing familial hemophagocytic lymphohistiocytosis type 4 (FHL-4). In several FHL-4 patients, we also observed hypogammaglobulinemia, elevated frequencies of naive B cells, and increased double-negative DN2:DN1 B cell ratios, indicating a hitherto unrecognized role of STX11 in humoral immunity...

Despite advances in treatment strategies, colorectal cancer (CRC) continues to cause significant morbidity and mortality, with mounting evidence a close link between immune system dysfunctions issued. Interleukin-2 receptor gamma (IL-2RG) plays a pivotal role as a common subunit receptor in the IL-2 family cytokines and activates the JAK-STAT pathway. This study delves into the role of Interleukin-2 receptor gamma (IL-2RG) within the tumor microenvironment and investigates potential microRNAs (miRNAs) that directly inhibit IL-2RG, aiming to discern their impact on CRC clinical outcomes...

Diabetic retinopathy is a microvascular disease that causes blindness. Using acid sphingomyelinase knockout mice, we reported that ceramide generation is critical for diabetic retinopathy development. Here, in patients with proliferative diabetic retinopathy, we identify vitreous ceramide imbalance with pathologic long-chain C16-ceramides increasing and protective very long-chain C26-ceramides decreasing. C16-ceramides generate pro-inflammatory/pro-apoptotic ceramide-rich platforms on endothelial surfaces. To geo-localize ceramide-rich platforms, we invented a three-dimensional confocal assay and showed that retinopathy-producing cytokines TNFα and IL-1β induce ceramide-rich platform formation on retinal endothelial cells within seconds, with volumes increasing 2-logs, yielding apoptotic death...

RATIONALE: Bronchiectasis is characterised by acute exacerbations but the biological mechanisms underlying these events is poorly characterised. Objectives To investigate the inflammatory and microbial characteristics of exacerbations of bronchiectasis. METHODS: 120 patients with bronchiectasis were enrolled and presented with acute exacerbations within 12 months. Spontaneous sputum samples were obtained during a period of clinical stability and again at exacerbation prior to receipt of antibiotic treatment...

BACKGROUND: Maternal-fetal immunology is intricate, and the effects of mRNA-S maternal vaccination on immune regulation at the maternal-fetal interface require further investigation. Our study endeavors to elucidate these immunological changes, enhancing our comprehension of maternal and fetal health outcomes. By analyzing immune profiles and cytokine responses, we aim to provide valuable insights into the impact of mRNA-S vaccination on the delicate balance of immune regulation during pregnancy, addressing critical questions in the field of reproductive pharmacology...

BACKGROUND: Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening syndrome characterized by excessive immune activation and inflammatory response. Conventional immunotherapy and molecular targeted drugs demonstrate varying efficacy. Cytokine storm, the primary pathogenic mechanism of HLH, is driven by interferon-gamma (IFN-γ), interleukin (IL)-2, IL-18, etc., in which IFN-γ plays a critical role in the development of the disease. Emapalumab, a potent IFN-γ inhibitor, effectively reduces the occurrence of cytokine storms in refractory and relapsed HLH...

BACKGROUND: Interleukin-6 (IL-6) is a multifunctional cytokine that controls the immune response, and its role has been described in the development of autoimmune diseases. Signaling via its cognate IL-6 receptor (IL-6R) complex is critical in tumor progression and, therefore, IL-6R represents an important therapeutic target. METHODS: An albumin-binding domain-derived highly complex combinatorial library was used to select IL-6R alpha (IL-6Rα)-targeted small protein binders using ribosome display...

BACKGROUND: To explore the alterations of inflammatory markers and immune-related cytokines in children infected with Mycoplasma pneumoniae (MP) combined with Adenovirus (ADV). METHODS: The study population consisted of 201 children with MPP, and they were grouped according to whether they were coinfected with ADV infection and critically ill. Additionally, comparative analyses were performed. The diagnostic value of different indicators and combined indicators for SMPP combined with ADV was assessed using ROC curves...

BACKGROUND: Inflammation is implicated in cardiovascular disease (CVD) pathogenesis, but causal roles of specific circulating inflammatory cytokines remain unclear. Mendelian randomization (MR) studies are well-poised to provide etiological insights beyond constraints of conventional research. METHODS: We conducted a large-scale MR study to investigate potential causal relationships of 91 inflammatory proteins with CVD outcomes and cardiac remodeling using summary-level genetic data...

INTRODUCTION: Pemphigus, an uncommon autoimmune blistering disorder affecting the skin and mucous membranes, currently with mortality primarily attributed to adverse reactions resulting from treatment protocols. Additionally, the existing treatments exhibit a notable recurrence rate. The high incidence of relapse and the considerable adverse effects associated with treatment underscore the imperative to explore safer and more effective therapeutic approaches. Numerous potential therapeutic targets have demonstrated promising outcomes in trials or preliminary research stages...

Interleukin 2 (IL-2) is the first identified cytokine and its interaction with receptors has been known to shape the immune responses in many lymphoid or non-lymphoid tissues for more than four decades. Active T cells are the primary cellular source for IL-2 production and epithelial cells have never been considered the major cellular source of IL-2 under physiological conditions. It is, however, tempting to speculate that epithelial cells could potentially express IL-2 that regulates the intricate interactions between epithelial cells and lymphocytes...

Antigen specificity is the central trait distinguishing adaptive from innate immune function. Assembly of antigen-specific T cell and B cell receptors occurs through V(D)J recombination mediated by the Recombinase Activating Gene endonucleases RAG1 and RAG2 (collectively called RAG). In the absence of RAG, mature T and B cells do not develop and thus RAG is critically associated with adaptive immune function. In addition to adaptive T helper 2 (Th2) cells, group 2 innate lymphoid cells (ILC2s) contribute to type 2 immune responses by producing cytokines like Interleukin-5 (IL-5) and IL-13...

BACKGROUND: The formation of shoots plays a pivotal role in plant organogenesis and productivity. Despite its significance, the underlying molecular mechanism of de novo regeneration has not been extensively elucidated in Capsicum annuum 'Dempsey', a bell pepper cultivar. To address this, we performed a comparative transcriptome analysis focusing on the differential expression in C. annuum 'Dempsey' shoot, callus, and leaf tissue. We further investigated phytohormone-related biological processes and their interacting genes in the C...

Cadmium telluride (CdTe) quantum dots (QDs) have garnered significant attention for tumor imaging due to their exceptional properties. However, there remains a need for further investigation into their potential toxicity mechanisms and corresponding enhancements. Herein, CdTe QDs were observed to accumulate in mouse liver, leading to a remarkable overproduction of IL-1β and IL-6. Additionally, there was evidence of macrophage infiltration and activation following exposure to 12.5 μmol/kg body weight of QDs...

PURPOSE: Early diagnosis of surgical site infections (SSIs) could prevent surgical revision. Inflammatory markers (IMs), such as procalcitonin (PCT), interleukin-6 (IL-6), and tumor necrosis factor α (TNF-α), seem more accurate in diagnosing SSI than C-reactive protein (CRP) and white blood cell (WBC) count. The aim was to compare the predictive values of CRP, WBC count, PCT, IL-6, and TNF-α in SSI detection. METHODS: A total of 130 patients undergoing dorsal spondylodesis from 2019 to 2024 were enrolled in a prospective diagnostic study at a maximum care spine center...

Childhood obesity is a chronic inflammatory epidemic that affects children worldwide. Obesity affects approximately 1 in 5 children worldwide. Obesity in children can worsen weight gain and raise the risk of obesity-related comorbidities like diabetes and non-alcoholic fatty liver disease (NAFLD). It can also negatively impact the quality of life for these children. Obesity disrupts immune system function, influencing cytokine (interleukins) balance and expression levels, adipokines, and innate and adaptive immune cells...

Chronic life-threatening ischemia (CLTI), characterized by chronic severe ischemic ulcers or gangrene in the legs with arterial occlusive disease, has a high rate of amputation and mortality. However, how lower extremity artery disease (LEAD) leads to CLTI is not fully understood yet. Here, we report a 79-year-old man with resting pain and gangrene in the left first and fifth toes for a year who had undergone repetitive endovascular treatment (EVT) that temporarily improved the ischemia. Non-obstructive general angioscopy (NOGA) revealed yellow and red floating emboli at the occluded left superficial femoral artery (SFA)...

Background Saliva and blood, being biological materials with a high potential for infectious transmission in dental environments, pose significant risks to dental professionals, assistants, and patients alike. Therefore, practitioners must adopt stringent security measures to ensure patient care, considering all parties as potential carriers of microorganisms capable of causing infectious diseases. Currently, various methods of disinfection and sterilization are employed to maintain the aseptic chain effectively...

BACKGROUND: Psoriasis is an inflammatory skin disease characterized by the hyperproliferative epidermal keratinocytes and significant immune cells infiltration, leading to cytokines production such as IL-1β, TNF-α, IL-23, and IL-17. Recent study highlights the critical role of IL-1β in the induction and activation of pathogenic Th17 and IL-17-producing γδ T cells, contributing to psoriasis. However, the mechanism underlying IL-1β dysregulation in psoriasis pathogenesis is unclear...

The human pathogen Neisseria gonorrhoeae ascends into the upper female reproductive tract to cause damaging inflammation within the Fallopian tubes and pelvic inflammatory disease (PID), increasing the risk of infertility and ectopic pregnancy. The loss of ciliated cells from the epithelium is thought to be both a consequence of inflammation and a cause of adverse sequelae. However, the links between infection, inflammation, and ciliated cell extrusion remain unresolved. With the use of ex vivo cultures of human Fallopian tube paired with RNA sequencing we defined the tissue response to gonococcal challenge, identifying cytokine, chemokine, cell adhesion, and apoptosis related transcripts not previously recognized as potentiators of gonococcal PID...