IQGAP1 Influences Neutrophil Maturation and Its Effector Functions.

IQ motif containing GTPase activating protein 1 (IQGAP1) is a protein scaffold that integrates signals regulating various cellular functions. Recently, utilizing proteomics as a discovery tool and co-immunoprecipitation as a validation method, we reported IQGAP1 as a potential ligand for CD11c, an adhesion molecule that was highly expressed in the intracellular components of neutrophils and regulated the maturation, survival, and function of neutrophils. To date, the role of IQGAP1 in inflammation and immune response is largely unknown.

Neutrophil extracellular traps formation is associated with postoperative complications in congenital cardiac surgery.

Backgrounds: Pediatric patients with congenital heart disease (CHD) often require surgical repair using cardiopulmonary bypass. Despite advancements, mortality and complication rates remain significant.

Methods & Results: We prospectively examined 101 patients undergoing congenital cardiac surgery, identifying a mortality rate of 4.

Pilot-scale and large-scale Fenton-like applications with nano-metal catalysts: From catalytic modules to scale-up applications.

Recently, great efforts have been made to advance the pilot-scale and engineering-scale applications of Fenton-like processes using various nano-metal catalysts (including nanosized metal-based catalysts, smaller nanocluster catalysts, and single-atom catalysts, etc.). This step is essential to facilitate the practical applications of advanced oxidation processes (AOPs) for these highly active nano-metal catalysts.

Mechanism of isoflurane‑mediated breast cancer growth .

Use of volatile anesthetics is associated with worse outcome following tumor resection surgery compared with the use of intravenous anesthetics. However, the underlying mechanism has not been clearly delineated yet . The EO771 cell-based congenic breast cancer model was used in the present study.

Integrin CD11c regulates B cell homeostasis.

CD11c is widely known as a cell surface marker for dendritic cells, but we recently showed that it regulates neutrophil and T cell functions. Because we found that CD11c knockout (KO) mice had lower blood B cell counts, we characterized B cell profile in developmental stages. We found that CD11c KO recirculating and mature B cells was significantly fewer compared with wild type, associated with exaggerated proliferation and apoptosis.

Neutrophil extracellular traps formation is associated with postoperative complications in neonates and infants undergoing congenital cardiac surgery.

Unlabelled: Pediatric patients with congenital heart diseases (CHD) often undergo surgical repair on cardiopulmonary bypass (CPB). Despite a significant medical and surgical improvement, the mortality of neonates and infants remains high. Damage-associated molecular patterns (DAMPs) are endogenous molecules released from injured/damaged tissues as danger signals.

CD11a regulates hematopoietic stem and progenitor cells.

Integrin αLβ2 (CD11a/CD18, CD11a) is a critical leukocyte adhesion molecule in leukocyte arrest and immunological synapse formation. However, its role in the bone marrow has not been investigated in depth. Here we showed that CD11a was expressed on all subsets of hematopoietic stem and progenitor cells (HPSCs).

Effects of Curcuminoids and Surfactant-Formulated Curcumin on Chemo-Resistant Colorectal Cancer.

Colorectal cancer (CRC) is a leading cause of cancer-related death in the United States, and chronic gut inflammation is a risk factor for CRC initiation and development. L., or turmeric, has become one of the most studied herbal medicines in recent years due to its anticancer potentials.

αDβ2 as a novel target of experimental polymicrobial sepsis.

Since sepsis was defined three decades ago, it has been a target of intensive study. However, there is no specific sepsis treatment available, with its high mortality and morbidity. αDβ2 (CD11d/CD18) is one of the four β2 integrin members.

CD11c regulates late-stage T cell development in the thymus.

CD11c, also named integrin αX, has been deemed solely as a dendritic cell marker for decades while the delineation of its biological function was limited. In the current study, we observed in mice that CD11c deficiency led to a defect in T cell development, demonstrated by the loss of CD4CD8 double positive (DP) T cells, CD4CD8, and CD4CD8 single positive (SP) T cells in the thymus and less mature T cells in the periphery. By using bone marrow chimera, we confirmed that CD11c regulated T cell development in the thymus.

CD11c regulates neutrophil maturation.

Sepsis continues to be associated with high morbidity and mortality. Currently, sepsis is managed only conservatively. In sepsis, a substantial number of neutrophils is required, leading to accelerated neutrophil production.

The transcription factor FoxP3 can fold into two dimerization states with divergent implications for regulatory T cell function and immune homeostasis.

FoxP3 is an essential transcription factor (TF) for immunologic homeostasis, but how it utilizes the common forkhead DNA-binding domain (DBD) to perform its unique function remains poorly understood. We here demonstrated that unlike other known forkhead TFs, FoxP3 formed a head-to-head dimer using a unique linker (Runx1-binding region [RBR]) preceding the forkhead domain. Head-to-head dimerization conferred distinct DNA-binding specificity and created a docking site for the cofactor Runx1.

Measurement of Time-Dependent Drive Flux on the Capsule for Indirectly Driven Inertial Confinement Fusion Experiments.

A new method for measuring the time-dependent drive flux at the hohlraum center is proposed as a better alternative to conventional wall-based techniques. The drive flux here is obtained by simultaneous measurement of the reemitted flux and shock velocity from a three-layered "cakelike" sample. With these two independent observables, the influence induced by the uncertainty of the material parameters of the sample can be effectively decreased.

CCR6 and CXCR6 Identify the Th17 Cells With Cytotoxicity in Experimental Autoimmune Encephalomyelitis.

Due to the plasticity of IL-17-producing CD4 T cells (Th17 cells), a long-standing challenge in studying Th17-driven autoimmune is the lack of specific surface marker to identify the pathogenic Th17 cells . Recently, we discovered that pathogenic CD4 T cells were CXCR6 positive in experimental autoimmune encephalomyelitis (EAE), a commonly used Th17-driven autoimmune model. Herein, we further revealed that peripheral CXCR6CD4 T cells contain a functionally distinct subpopulation, which is CCR6 positive and enriched for conventional Th17 molecules (IL-23R and RORγt) and cytotoxic signatures.

Effects of dihydroartemisinin, a metabolite of artemisinin, on colon cancer chemoprevention and adaptive immune regulation.

Background: Artemisinin (ART) is an anti-malaria natural compound with a moderate anticancer action. As a metabolite of ART, dihydroartemisinin (DHA) may have stronger anti-colorectal cancer (CRC) bioactivities. However, the effects of DHA and ART on CRC chemoprevention, including adaptive immune regulation, have not been systematically evaluated and compared.

Anesthetics isoflurane and sevoflurane attenuate flagellin-mediated inflammation in the lung.

Isoflurane and sevoflurane are volatile anesthetics (VA) widely used in clinical practice to provide general anesthesia. We and others have previously shown that VAs have immunomodulatory effects and may have a significant impact on the progression of disease states. Flagellin is a component of Gram negative bacteria and plays a significant role in the pathophysiology of bacterial pneumonia through its binding to Toll-like Receptor 5 (TLR5).

Cathepsin L regulates pathogenicCD4 T cells in experimental autoimmune encephalomyelitis.

Previously we reported that IL-17-producing CD4 T cells (Th17) were increased in mice lacking the protease inhibitor SerpinB1 and several SerpinB1-inhibitable cysteine cathepsins were induced in the Th17 cells, most prominently cathepsin L (CtsL). Since CtsL also mediates invariant chain processing in thymic epithelial cells, deficiency of CtsL leads to impaired CD4 T cell thymic selection, which hinders the direct investigation of CD4 T cells in CtsL mouse. In the current study, through transplanting the CtsL bone marrow into lethally irradiated CtsL-sufficient Rag mice (bone marrow chimeras), we reconstituted the immune system of CtsL chimeric mice, which possessed normal CD4 T cell development and allowed us to study the intrinsic role of CtsL in CD4 T cells in Th17 cell-driven autoimmune diseases.

The Microbial Flora in an Experimental Polymicrobial Abdominal Sepsis Model Probed by 16S rRNA Sequencing.

Background: Cecal ligation and puncture (CLP) surgery is a widely used preclinical model to induce and study sepsis because it is considered to recapitulate the course of human sepsis the most. This model is highly dependent on the polymicrobial gut flora and represents polymicrobial abdominal sepsis. While the majority of studies using CLP model have focused on the delineation of host immune responses, a limited number of reports have described the composition of microbial strains in this model, although microbial composition can significantly affect the outcome of sepsis in general.

CD11c regulates hematopoietic stem and progenitor cells under stress.

β2 integrins are well-known leukocyte adhesion molecules consisting of 4 members: CD11a-d. Their known biological functions range widely from leukocyte recruitment, phagocytosis, to immunological synapse formation, but the studies have been primarily focused on CD11a and CD11b. CD11c is 1 of the 4 members and is extremely homologous to CD11b.

Mechanistic consideration of the effect of perioperative volatile anesthetics on phagocytes.

A growing literature has shown that volatile anesthetics are promiscuous molecules targeting multiple molecules, some of which are critical for immunological functions. We focused on studies that delineated target molecules of volatile anesthetics on immune cells and summarized the effects of volatile anesthetics on immune functions. We also presented the perspectives of studying volatile anesthetics-mediated immunomodulation.

Role of β2 Integrins in Neutrophils and Sepsis.

Sepsis remains medically challenging, with high morbidity and mortality. A novel intervention is urgently needed in the absence of specific, targeted therapy. Neutrophils act as double-edged swords in sepsis; they can help to eradicate microbes, but they also contribute to tissue injury.

Volatile Anesthetic Sevoflurane Attenuates Toll-Like Receptor 1/2 Activation.

Background: Although immunomodulatory effects of anesthetics have been increasingly recognized, their underlying molecular mechanisms are not completely understood. Toll-like receptors (TLRs) are one of the major receptors to recognize invading pathogens and danger signals from damaged host tissues to initiate immune responses. Among the TLR family, TLR2 and TLR4 recognize a wide range of ligands and are considered to be important players in perioperative pathophysiology.