N-acetyl-L-alanine ameliorates atopic dermatitis-like symptoms by suppressing Th2 differentiation in DNFB-induced NC/Nga mice.

Atopic dermatitis (AD) is a chronic dermatological disorder characterized by intense pruritus and eczematous lesions. Repeated topical application of 2,4-dinitrofluorobenzene (DNFB) in NC/Nga mice produces AD-like clinical symptoms that closely resemble human AD. N-Acetyl-L-Alanine (L-NAA), a derivative of L-Alanine, has unknown biological and physiological effects on cutaneous tissue.

Persistent Activation of Sphingosine-1-Phosphate Receptor 1 by Phytosphingosine-3,4-Cyclic Phosphate Ameliorates Sepsis by Inhibiting Hyperinflammation and Vascular Hyperpermeability.

Sepsis is a life-threatening disease characterized by multiorgan dysfunction caused by an abnormal immune response to microbial infection. Sphingosine-1-phosphate (S1P) levels are significantly lower in patients with sepsis and are negatively correlated with the severity of sepsis. However, whether the S1P signaling pathway is a target for sepsis treatment remains unknown.

The HRAS-binding C2 domain of PLCη2 suppresses tumor-like synoviocytes and experimental arthritis in rheumatoid arthritis.

Fibroblast-like synoviocytes (FLSs), which are stromal cells that play key roles in rheumatoid arthritis (RA) pathophysiology, are characterized by a tumor-like phenotype and immunostimulatory actions. C2 domains in various proteins play roles in intracellular signaling and altering cellular characteristics, and some C2 domain-containing proteins exacerbate or alleviate certain malignant or inflammatory diseases. However, the roles of C2 domains in regulating the functions of RA FLSs remain unclear.

Strong intramolecular charge-transfer effect strengthening naphthoquinone-based chemosensor: Experimental and theoretical evaluation.

An aminophenol-linked naphthoquinone-based fluorometric and colorimetric chemosensor 2-chloro-3-((3-hydroxyphenyl) amino) naphthalene-1,4-dione (2CAN-Dione) was synthesized for selective detection of Sn ion in aqueous solution. The amine and conversion of carbonyl into carboxyl groups play a vital role in the sensing mechanism when Sn is added to 2CAN-Dione. Comprehensive characterization of the sensor was carried out using standard spectral and analytical approaches.

Interferon-β alleviates sepsis by SIRT1-mediated blockage of endothelial glycocalyx shedding.

Sepsis is a life-threatening multi-organ dysfunction with high mortality caused by the body's improper response to microbial infection. No new effective therapy has emerged that can adequately treat patients with sepsis. We previously demonstrated that interferon-β (IFN-β) protects against sepsis via sirtuin 1-(SIRT1)-mediated immunosuppression.

Glutamine deficiency shifts the asthmatic state toward neutrophilic airway inflammation.

Background: The administration of L-glutamine (Gln) suppresses allergic airway inflammation via the rapid upregulation of MAPK phosphatase (MKP)-1, which functions as a negative regulator of inflammation by deactivating p38 and JNK mitogen-activated protein kinases (MAPKs). However, the role of endogenous Gln remains to be elucidated. Therefore, we investigated the mechanism by which endogenous Gln regulates MKP-1 induction and allergic airway inflammation in an ovalbumin-based murine asthma model.

MUC1-C Contributes to the Maintenance of Human Embryonic Stem Cells and Promotes Somatic Cell Reprogramming.

Mucin 1 (MUC1) is a transmembrane glycoprotein overexpressed in several cancer cells in which it regulates cell surface properties, tumor invasion, and cell death. Recently, we reported that MUC1-C, the C-terminal subunit of MUC1, is involved in the growth of mouse embryonic stem (ES) cells. However, the functional significance of MUC1-C in human ES cells remains unclear.

Mitochondria-targeted acridine-based dual-channel fluorescence chemosensor for detection of Sn and CrO ions in water and its application in discriminative detection of cancer cells.

The goal of the present work was to fabricate a new low-cost, easy-to-prepare, dual-channel fluorescence chemosensor comprised of acridine-diphenylacetyl moieties (NDA) to enable remarkable Sn detection in water and biological medium. The resulting NDA-Sn complex was utilized for the distinguished identification of CrO ions from other anions and biomolecules. These investigations involve the absorption, fluorescence, and electrochemical methods for the detection of Sn and CrO ions in pure water.

A dual-channel colorimetric and ratiometric fluorescence chemosensor for detection of Hg ion and its bioimaging applications.

A new colorimetric and ratiometric fluorescence chemosensor 4-((3-(octadecylthio)-1,4-dioxo-1,4-dihydronaphthalen-2-yl)amino)benzenesulfonamide (4DBS) was synthesized and investigated for the selective detection of Hg in DMSO-HO (9:1, v/v) solution. The chemosensor was efficiently synthesized in two steps via Michael-like addition and nucleophilic substitution reactions. The ratiometric fluorescence turn-on response was obtained towards Hg, and its fluorescence emission peak was red-shifted by 140 nm with an associated color change from light maroon to pale yellow due to the intramolecular charge transfer effect.

Changes in the phosphorylation of nucleotide metabolism‑associated proteins by leukemia inhibitory factor in mouse embryonic stem cells.

Leukemia inhibitory factor (LIF) is a stem cell growth factor that maintains self‑renewal of mouse embryonic stem cells (mESCs). LIF is a cytokine in the interleukin‑6 family and signals via the common receptor subunit gp130 and ligand‑specific LIF receptor. LIF causes heterodimerization of the LIF receptor and gp130, activating the Janus kinase/STAT and MAPK pathways, resulting in changes in protein phosphorylation.

Mitochondria-targeted dual-channel colorimetric and fluorescence chemosensor for detection of Sn ions in aqueous solution based on aggregation-induced emission and its bioimaging applications.

Several fluorescence and colorimetric chemosensory for Sn detection in an aqueous media have been reported, but applications remain limited for discriminative Sn detection in live human cells and zebrafish larvae. Herein, a mitochondria-targeted Sn "turn-on" colorimetric and fluorescence chemosensor, 2CTA, with an aggregation-induced emission (AIE) response was developed. The sensing of Sn was enabled by a reduction-enabled binding pathway, with the conversion of -C˭O groups to -C-OH groups at the naphthoquinone moiety.

Simple Colorimetric and Fluorescence Chemosensing Probe for Selective Detection of Sn Ions in an Aqueous Solution: Evaluation of the Novel Sensing Mechanism and Its Bioimaging Applications.

An easily accessible colorimetric and fluorescence probe 4-((3-chloro-1,4-dioxo-1,4-dihydronaphthalen-2-yl)amino)benzenesulfonamide () was successfully developed for the selective and sensitive detection of Sn in an aqueous solution. The sensing mechanism involves reduction of -C═O into -C-OH groups in upon the addition of Sn, which initiates the fluorescence turn-on mode. A better linear relationship was achieved between fluorescence intensity and Sn concentration in the range of 0-62.

Inhibition of MUC1-C Increases ROS and Cell Death in Mouse Embryonic Stem Cells.

Background And Objectives: Embryonic stem (ES) cells have the capacity to self-renew and generate all types of cells. MUC1-C, a cytoplasmic subunit of MUC1, is overexpressed in various carcinomas and mediates signaling pathways to regulate intracellular metabolic processes and gene expression involved in the maintenance of cancer cells. However, the functional role of MUC1-C in ES cells is not well understood.

SIRT1 induces the adipogenic differentiation of mouse embryonic stem cells by regulating RA-induced RAR expression via NCOR1 acetylation.

SIRT1 (NAD-dependent deacetylase) plays a suppressive role during the late stages of adipogenesis. However, the effects of SIRT1 on the early phases of adipogenic differentiation from embryonic stem cells (ESCs) are poorly understood. We employed Sirt1 and Sirt1 mouse embryonic stem cells (mESCs) to evaluate the role of SIRT1 during the early stage mESC differentiation to adipocytes in response to retinoic acid (RA) treatment.

SIRT1 Knockdown Enhances the Differentiation of Human Embryonic Stem Cells into Pancreatic β Cells.

Nicotinamide is used to maturate pancreatic progenitors from embryonic stem cells (ESCs) into insulin-producing cells (IPCs). It has been known that nicotinamide inhibits the enzymatic activity of SIRT1, an NAD-dependent deacetylase. Here we show that SIRT1 knockdown enhances the differentiation of human ESCs into IPCs.

Synthesis and Antimicrobial Evaluation of 1,4-Naphthoquinone Derivatives as Potential Antibacterial Agents.

1,4-Naphthoquinones are an important class of compounds present in a number of natural products. In this study, a new series of 1,4-naphthoquinone derivatives were synthesized. All the synthesized compounds were tested for antimicrobial activity.

Splitomicin, a SIRT1 Inhibitor, Enhances Hematopoietic Differentiation of Mouse Embryonic Stem Cells.

Background And Objectives: Embryonic stem (ES) cells have pluripotent ability to differentiate into multiple tissue lineages. SIRT1 is a class III histone deacetylase which modulates chromatin remodeling, gene silencing, cell survival, metabolism, and development. In this study, we examined the effects of SIRT1 inhibitors on the hematopoietic differentiation of mouse ES cells.

HSP60 is required for stemness and proper differentiation of mouse embryonic stem cells.

Embryonic stem cells (ESCs) are metabolically distinct from their differentiated counterparts. ESC mitochondria are less complex and fewer in number than their differentiated progeny. However, few studies have examined the proteins responsible for differences in mitochondrial structure and function between ESCs and somatic cells.

GPCR Kinase (GRK)-2 Is a Key Negative Regulator of Itch: l-Glutamine Attenuates Itch via a Rapid Induction of GRK2 in an ERK-Dependent Way.

Many itch mediators activate GPCR and trigger itch via activation of GPCR-mediated signaling pathways. GPCRs are desensitized by GPCR kinases (GRKs). The aim of this study is to explore the role of GRKs in itch response and the link between GRKs and glutamine, an amino acid previously shown to be an itch reliever.

Suppression of the ERK-SRF axis facilitates somatic cell reprogramming.

The molecular mechanism underlying the initiation of somatic cell reprogramming into induced pluripotent stem cells (iPSCs) has not been well described. Thus, we generated single-cell-derived clones by using a combination of drug-inducible vectors encoding transcription factors (Oct4, Sox2, Klf4 and Myc) and a single-cell expansion strategy. This system achieved a high reprogramming efficiency after metabolic and epigenetic remodeling.

Effects of mechanical stimulation on the reprogramming of somatic cells into human-induced pluripotent stem cells.

Background: Mechanical stimuli play important roles in the proliferation and differentiation of adult stem cells. However, few studies on their effects on induced pluripotent stem cells (iPSCs) have been published.

Methods: Human dermal fibroblasts were seeded onto flexible membrane-bottom plates, and infected with retrovirus expressing the four reprogramming factors OCT4, SOX2, KLF, and c-MYC (OSKM).

Protein tyrosine phosphatase 1B is a mediator of cyclic ADP ribose-induced Ca signaling in ventricular myocytes.

Cyclic ADP-ribose (cADPR) releases Ca from ryanodine receptor (RyR)-sensitive calcium pools in various cell types. In cardiac myocytes, the physiological levels of cADPR transiently increase the amplitude and frequency of Ca (that is, a rapid increase and decrease of calcium within one second) during the cardiac action potential. In this study, we demonstrated that cADPR levels higher than physiological levels induce a slow and gradual increase in the resting intracellular Ca ([Ca]) level over 10 min by inhibiting the sarcoendoplasmic reticulum Ca ATPase (SERCA).

Platelet-activating Factor Mediates Endotoxin Tolerance by Regulating Indoleamine 2,3-Dioxygenase-dependent Expression of the Suppressor of Cytokine Signaling 3.

Indoleamine 2,3-dioxygenase (IDO) mediates immune tolerance, and suppressor of cytokine signaling 3 (SOCS3) negatively regulates the JAK/STAT signal transduction pathway. We determined previously that platelet-activating factor (PAF) protects mice against LPS-induced endotoxic shock, but its detailed mechanism of action was unknown. We performed survival experiments in and mice using an LPS-induced endotoxemia model and rated organ injury (neutrophil infiltration and liver function).

Skin Aging-Dependent Activation of the PI3K Signaling Pathway via Downregulation of PTEN Increases Intracellular ROS in Human Dermal Fibroblasts.

Reactive oxygen species (ROS) play a major role in both chronological aging and photoaging. ROS induce skin aging through their damaging effect on cellular constituents. However, the origins of ROS have not been fully elucidated.