Metabolic Reprogramming of Phospholipid Fatty Acids as a Signature of Lung Cancer Type.

Lung cancer is one of the leading causes of cancer-related mortality. Non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC) differ in aggressiveness, proliferation speed, metastasis propensity, and prognosis. Since tumor cells notably change lipid metabolism, especially phospholipids and fatty acids (FA), this study aimed to identify FA alterations in lung cancer tissues.

Hyperbranched, Functional Polyethoxysiloxanes: Tunable Molecular Building Blocks.

Functional silanes are multifaceted cross-linkers, compatibilizers, coupling agents, and surface modifiers. Herein, we present organofunctional polysiloxane building blocks that offer great versatility in terms of molecular weight, degree of condensation, and the choice and loading of organic substituent groups. The organofunctional polyethoxysilanes (funPEOS) are prepared in a one-pot, two-step process: synthesis of the PEOS carrier/substrate, followed by grafting a functional silane "shell", both based on condensation with acetic anhydride.

Lifelong development in medicine: a thematic analysis of coaching goals throughout medical careers.

Objectives: Healthcare grapples with staff shortages and rising burnout rates for medical students, residents and specialists. To prioritise both their well-being and the delivery of high-quality patient care, it becomes imperative to deepen our understanding of physicians' developmental aims and needs. Our first aim is, therefore, to gain comprehensive insights into the specific developmental aims physicians prioritise by examining the coaching goals they set at the beginning of coaching.

Vitamin A-treated natural killer cells reduce interferon-gamma production and support regulatory T-cell differentiation.

Natural killer (NK) cells are innate cytotoxic lymphocytes that contribute to immune responses against stressed, transformed, or infected cells. NK cell effector functions are regulated by microenvironmental factors, including cytokines, metabolites, and nutrients. Vitamin A is an essential micronutrient that plays an indispensable role in embryogenesis and development, but was also reported to regulate immune responses.

Herb-Induced Liver Injury by Ayurvedic Ashwagandha as Assessed for Causality by the Updated RUCAM: An Emerging Cause.

Herb-induced liver injury (HILI) caused by herbal supplements, natural products, and products used in traditional medicine are important for differential diagnoses in patients with acute liver injury without an obvious etiology. The root of (L.) Dunal, commonly known as ashwagandha, has been used in Ayurvedic medicine for thousands of years to promote health and longevity.

Liver sinusoidal endothelial cells orchestrate NK cell recruitment and activation in acute inflammatory liver injury.

Liver sinusoidal endothelial cells (LSECs) rapidly clear lipopolysaccharide (LPS) from the bloodstream and establish intimate contact with immune cells. However, their role in regulating liver inflammation remains poorly understood. We show that LSECs modify their chemokine expression profile driven by LPS or interferon-γ (IFN-γ), resulting in the production of the myeloid- or lymphoid-attracting chemokines CCL2 and CXCL10, respectively, which accumulate in the serum of LPS-challenged animals.

Lyve-1 deficiency enhances the hepatic immune microenvironment entailing altered susceptibility to melanoma liver metastasis.

Background: Hyaluronan receptor LYVE-1 is expressed by liver sinusoidal endothelial cells (LSEC), lymphatic endothelial cells and specialized macrophages. Besides binding to hyaluronan, LYVE-1 can mediate adhesion of leukocytes and cancer cells to endothelial cells. Here, we assessed the impact of LYVE-1 on physiological liver functions and metastasis.

Targeting of Scavenger Receptors Stabilin-1 and Stabilin-2 Ameliorates Atherosclerosis by a Plasma Proteome Switch Mediating Monocyte/Macrophage Suppression.

Background: Scavenger receptors Stabilin-1 (Stab1) and Stabilin-2 (Stab2) are preferentially expressed by liver sinusoidal endothelial cells. They mediate the clearance of circulating plasma molecules controlling distant organ homeostasis. Studies suggest that Stab1 and Stab2 may affect atherosclerosis.

Caspase-8 in endothelial cells maintains gut homeostasis and prevents small bowel inflammation in mice.

The gut has a specific vascular barrier that controls trafficking of antigens and microbiota into the bloodstream. However, the molecular mechanisms regulating the maintenance of this vascular barrier remain elusive. Here, we identified Caspase-8 as a pro-survival factor in mature intestinal endothelial cells that is required to actively maintain vascular homeostasis in the small intestine in an organ-specific manner.

Human ILC3 Exert TRAIL-Mediated Cytotoxicity Towards Cancer Cells.

Group 3 helper Innate Lymphoid Cells (ILC3s) are cytokine-producing lymphocytes that respond to stress signals released during disturbed tissue homeostasis and infection. Upon activation, ILC3s secrete IL-22 and IL-17, and orchestrate immune responses against extracellular pathogens. Their role in cancer remains poorly explored.

Innate-like NKp30CD8 T cells armed with TCR/CAR target tumor heterogeneity.

Intratumoral heterogeneity is frequently associated with tumor immune escape, with MHC-class I and antigen expression loss rendering tumor cells invisible to T cell killing, representing a major challenge for the design of successful adoptive transfer protocols for cancer immunotherapy. While CD8 T cell recognition of tumor cells is based on the detection of MHC-peptide complexes via specific T cell receptors (TCRs), Natural Killer (NK) cells detect tumor-associated NK ligands by an array of NK receptors. We have recently identified a population of innate-like CD8 T cells marked by the expression of NKp30, a potent natural cytotoxicity activating NK receptor, whose tumor ligand, B7H6, is frequently upregulated on several cancer types.

ILC1-like NK cells as matchmakers for DC-T cell interactions.

Both innate and adaptive immunity are orchestrated by multiple cell types, specialized cell lineages, and their spatiotemporal encounters. It is thought that adaptive-like NK cell responses to viral infection mainly involve circulating bona fide NK cells. In this issue of Immunity, Flommersfeld et al.

An intimate encounter: DC3s empower anti-tumor CTLs.

Discrete tissue niches are emerging as essential prerequisites enabling cell communication and function in both homeostasis and disease. In a recent Cell paper, Di Pilato et al. identify a unique dendritic cell-cytotoxic T cell crosstalk within the perivascular space that facilitates T cell survival and proliferation and drives anti-tumor activity.

Development and Validation of a Multivariable Predictive Model for Mortality of COVID-19 Patients Demanding High Oxygen Flow at Admission to ICU: AIDA Score.

Introduction: Risk stratification is an important aspect of COVID-19 management, especially in patients admitted to ICU as it can provide more useful consumption of health resources, as well as prioritize critical care services in situations of overwhelming number of patients.

Materials And Methods: A multivariable predictive model for mortality was developed using data solely from a derivation cohort of 160 COVID-19 patients with moderate to severe ARDS admitted to ICU. The regression coefficients from the final multivariate model of the derivation study were used to assign points for the risk model, consisted of all significant variables from the multivariate analysis and age as a known risk factor for COVID-19 patient mortality.

Single-Cell RNA Sequencing of Tumor-Infiltrating NK Cells Reveals that Inhibition of Transcription Factor HIF-1α Unleashes NK Cell Activity.

Enhancing immune cell functions in tumors remains a major challenge in cancer immunotherapy. Hypoxia is a common feature of solid tumors, and cells adapt by upregulating the transcription factor HIF-1α. Here, we defined the transcriptional landscape of mouse tumor-infiltrating natural killer (NK) cells by using single-cell RNA sequencing.

Type 1 T cells promote the generation of CD8 tissue-resident memory T cells.

Tissue-resident memory T (T) cells, functionally distinct from circulating memory T cells, have a critical role in protective immunity in tissues, are more efficacious when elicited after vaccination and yield more effective antitumor immunity, yet the signals that direct development of T cells are incompletely understood. Here we show that type 1 regulatory T (T) cells, which express the transcription factor T-bet, promote the generation of CD8 T cells. The absence of T-bet-expressing type 1 T cells reduces the presence of T cells in multiple tissues and increases pathogen burden upon infectious challenge.

TGF-β2 silencing to target biliary-derived liver diseases.

Objective: TGF-β2 (TGF-β, transforming growth factor beta), the less-investigated sibling of TGF-β1, is deregulated in rodent and human liver diseases. Former data from bile duct ligated and MDR2 knockout (KO) mouse models for human cholestatic liver disease suggested an involvement of TGF-β2 in biliary-derived liver diseases.

Design: As we also found upregulated in liver tissue of patients with primary sclerosing cholangitis (PSC) and primary biliary cholangitis (PBC), we now fathomed the positive prospects of targeting TGF-β2 in early stage biliary liver disease using the MDR2-KO mice.

Distinct human circulating NKp30FcεRIγCD8 T cell population exhibiting high natural killer-like antitumor potential.

CD8 T cells are considered prototypical cells of adaptive immunity. Here, we uncovered a distinct CD8 T cell population expressing the activating natural killer (NK) receptor NKp30 in the peripheral blood of healthy individuals. We revealed that IL-15 could de novo induce NKp30 expression in a population of CD8 T cells and drive their differentiation toward a broad innate transcriptional landscape.

The NKG2D/NKG2DL Axis in the Crosstalk Between Lymphoid and Myeloid Cells in Health and Disease.

Natural killer group 2, member D (NKG2D) receptor is a type II transmembrane protein expressed by both innate and adaptive immune cells, including natural killer (NK) cells, CD8+ T cells, invariant NKT cells, γδ T cells, and some CD4+ T cells under certain pathological conditions. NKG2D is an activating NK receptor that induces cytotoxicity and production of cytokines by effector cells and supports their proliferation and survival upon engagement with its ligands. In both innate and T cell populations, NKG2D can costimulate responses induced by other receptors, such as TCR in T cells or NKp46 in NK cells.

Iron Induces Anti-tumor Activity in Tumor-Associated Macrophages.

Tumor-associated macrophages (TAMs) frequently help to sustain tumor growth and mediate immune suppression in the tumor microenvironment (TME). Here, we identified a subset of iron-loaded, pro-inflammatory TAMs localized in hemorrhagic areas of the TME. The occurrence of iron-loaded TAMs (iTAMs) correlated with reduced tumor size in patients with non-small cell lung cancer.

Early inflammatory players in cutanous fibrosis.

Systemic sclerosis (SSc) is one of the most complex systemic autoimmune diseases with multi-organ involvement and heterogeneous clinical manifestations. The exact etiology of SSc is still unknown. However, identified target structures are components of endothelial cells, the innate/adaptive immune systems and fibroblasts, resulting in the hallmarks of the disease in form of inflammation/autoimmunity, vasculopathy and fibrosis of the skin and internal organs.

Highly efficient IL-21 and feeder cell-driven expansion of human NK cells with therapeutic activity in a xenograft mouse model of melanoma.

Natural killer (NK) cells are promising antitumor effector cells, but the generation of sufficient NK cell numbers for adoptive immunotherapy remains challenging. Therefore, we developed a method for highly efficient expansion of human NK cells. expansion of NK cells in medium containing IL-2 and irradiated clinical-grade feeder cells (EBV-LCL) induced a 22-fold NK cell expansion after one week that was significantly increased to 53-fold by IL-21.

Antigen dependently activated cluster of differentiation 8-positive T cells cause perforin-mediated neurotoxicity in experimental stroke.

Neuroinflammation plays a key role in secondary brain damage after stroke. Although deleterious effects of proinflammatory cytokines are well characterized, direct cytotoxic effects of invading immune cells on the ischemic brain and the importance of their antigen-dependent activation are essentially unknown. Here we examined the effects of adaptive and innate immune cells-cytotoxic T lymphocytes (CTLs) and natural killer (NK) cells-that share the direct perforin-mediated cytotoxic pathway on outcome after cerebral ischemia in mice.